Serum irisin levels in new-onset type 2 diabetes.
Choi Yeon-Kyung,Kim Mi-Kyung,Bae Kwi Hyun,Seo Hyun-Ae,Jeong Ji-Yun,Lee Won-Kee,Kim Jung-Guk,Lee In-Kyu,Park Keun-Gyu
Diabetes research and clinical practice
AIMS:Irisin has been identified as a novel myokine that drives brown-fat-like conversion of white adipose tissue. In this cross-sectional study, we investigated whether serum irisin levels are decreased in patients with type 2 diabetes (T2D) compared with control subjects with normal glucose tolerance (NGT), and assessed the association between serum irisin levels and various metabolic parameters. METHODS:The study population was selected from a population-based study and included 104 subjects with NGT and 104 subjects with new-onset T2D. Serum irisin and adiponectin levels and metabolic parameters were measured. Multivariate logistic regression analysis was performed to assess the association between irisin levels and newly diagnosed T2D. RESULTS:Serum irisin levels were significantly decreased in the new-onset T2D group compared with the NGT control group (p=0.003). In a multivariable model adjusted for various metabolic parameters, increased irisin levels were associated with reduced odds (OR 0.64, 95% CI 0.47-0.88, p=0.006) of prevalent newly diagnosed T2D. Furthermore, multiple regression analysis showed that 2 h plasma glucose was an independent variable influencing serum irisin levels (p=0.004). CONCLUSION:In the present study, we found that serum irisin levels were decreased in T2D patients and inversely associated with newly diagnosed T2D, suggesting that irisin may play a crucial role in glucose intolerance and T2D.
Lower circulating irisin is associated with type 2 diabetes mellitus.
Liu Jian-Jun,Wong Melvin D S,Toy Wan Ching,Tan Clara S H,Liu Sylvia,Ng Xiao Wei,Tavintharan Subramaniam,Sum Chee Fang,Lim Su Chi
Journal of diabetes and its complications
AIMS:Irisin is a novel myokine secreted in response to PPAR-γ co-activator-1α (PGC-1α) activation. Earlier studies suggested that PGC-1α expression and activity were lower in myocytes in type 2 diabetes mellitus (T2DM). Therefore, we hypothesize that circulating irisin levels are lower in T2DM patients. METHODS:In this observational study, we recruited 96 T2DM subjects and 60 non-diabetic control subjects. Among T2DM subjects, 38% were on insulin treatment, 78% were taking statins and 72% were taking renin-angiotensin system antagonists. Circulating irisin was quantified by ELISA and its association with markers of metabolic phenotype was analyzed by Pearson bivariate correlation and multiple linear regression. RESULTS:Circulating irisin was significantly lower in individuals with T2DM compared with non-diabetic controls (T2DM 204 ± 72 ng/ml vs. non-diabetic control 257 ± 24 ng/ml, p < 0.0001). In non-diabetic subjects, circulating irisin was correlated with age (r = 0.398, p < 0.01), BMI (r = 0.387, p < 0.01), total cholesterol (r = 0.341, p < 0.01), total triglycerides (r = 0.299, p < 0.05), fasting blood glucose (r = 0.430, p < 0.01) and diastolic blood pressure (r = 0.306, p < 0.05). Multiple linear regression model revealed that BMI (β = 0.407, p = 0.012) and FBG (β = 0.315, p = 0.034) were associated with irisin in non-diabetic subjects after adjusting for multiple co-variates. However, similar analysis in T2DM subjects didn't reveal significant association between circulating irisin and major markers of metabolic phenotype. CONCLUSIONS:Circulating irisin is lower in T2DM compared with non-diabetic controls. Plasma irisin levels appear to be associated with important metabolic factors in non-diabetic subjects but not in individuals with type 2 diabetes.
Circulating irisin levels of prenatal and postnatal patients with gestational diabetes mellitus: A systematic review and meta-analysis.
Cui Lingling,Qiao Tianyi,Xu Fan,Li Zhonglei,Chen Tingting,Su Hongli,Chen Guixia,Zhang Li,Xu Dongmei,Zhang Xiaofeng
AIMS:At present, there are few studies on the relationship between circulating irisin levels and gestational diabetes mellitus (GDM), and the results are inconsistent. Therefore, this study conducts a systematic review and meta-analysis to comprehensively discuss the role of irisin in the occurrence and development of GDM. METHODS:We searched the articles on the relationship between GDM and circulating irisin levels up to September 2019, using the CNKI, WANFANG-DATA, PubMed and the Web of Science databases. RESULTS:Twenty two articles including 3563 participants were selected in the meta-analysis. Meta-analysis found the blood irisin levels for GDM group were significantly lower than that for control group during pregnancy(SMD = -0.88, 95%CI: -1.34, -0.42, P < 0.001). However, there was no significant difference of irisin levels in the postpartum blood and cord blood between the two groups (SMD = -1.44, 95 %CI: -3.79, 0.92, P = 0.23; SMD = -0.17, 95 %CI: -0.59, 0.25, P = 0.42, respectively). CONCLUSIONS:Compared with the control group, irisin levels in the GDM group during pregnancy are lower. However, it is no significant difference of irisin levels in the postpartum blood and cord blood. Irisin may play an important role in the occurrence and development of GDM, which needs further research to demonstrate.
Irisin as an early marker for predicting gestational diabetes mellitus: a prospective study.
Erol Onur,Erkal Neslihan,Ellidağ Hamit Yaşar,İsenlik Bekir Sıtkı,Aydın Özgür,Derbent Aysel Uysal,Yılmaz Necat
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
OBJECTIVE:The objective of this study is to evaluate maternal serum irisin levels in the first and second trimesters of pregnancy in women diagnosed with and without gestational diabetes mellitus (GDM). METHODS:We performed a prospective, nested case-control study in 258 pregnant women who were enrolled at the time of the first prenatal visit (6-11th weeks of gestation) and followed until delivery. Among the entire population, we selected 20 women who subsequently developed GDM and 30 women with uneventful pregnancies. Blood samples were collected once from each participant at 6-11th weeks of gestation during the fetal viability scan and at 24-28th weeks of gestation during screening for GDM. RESULTS:In the first trimester, irisin levels were significantly lower in women who later developed GDM (median = 453 ng/mL, range: 257-811 ng/mL) than in controls (median = 721 ng/mL, range: 700-786 ng/mL). In the second trimester, the difference in irisin levels between the GDM group (median = 749 ng/mL; range: 456-910 ng/mL) and controls (median = 757 ng/mL; range: 703-898 ng/mL) was not statistically significant. CONCLUSIONS:Irisin may be a useful biomarker in early pregnancy to predict the development of GDM.
High circulating irisin levels are associated with insulin resistance and vascular atherosclerosis in a cohort of nondiabetic adult subjects.
Sesti G,Andreozzi F,Fiorentino T V,Mannino G C,Sciacqua A,Marini M A,Perticone F
Irisin, a novel myokine, was proposed to be able to regulate glucose homeostasis and obesity in mice. Whether irisin levels are associated with cardio-metabolic variables, insulin sensitivity, and vascular atherosclerosis in humans remain unsettled. To determine the associations between circulating irisin levels, cardio-metabolic variables, insulin sensitivity, and common carotid intima-media thickness (IMT), an indicator of vascular atherosclerosis, a cross-sectional evaluation of circulating irisin levels and cardio-metabolic variables in 192 White adults was conducted. Insulin sensitivity and insulin clearance were assessed by euglycemic-hyperinsulinemic clamp. Common carotid IMT was measured by ultrasound. After adjusting for age and gender, irisin levels were positively correlated with body fat mass (r = 0.12, P < 0.05), fasting (r = 0.17, P < 0.01), 2 h post-load insulin (r = 0.15, P < 0.02) levels, and IMT (r = 0.29, P < 0.0001) and were negatively correlated with insulin-stimulated glucose disposal (r = -0.18, P = 0.007), Matsuda index (r = -0.13, P < 0.04), disposition index (r = -0.278, P < 0.0001), and insulin clearance (r = -0.26, P < 0.0001). After adjusting for age, gender, and BMI, individuals in the highest tertile of irisin levels exhibited higher body fat mass (P < 0.01), fasting (P < 0.05), 2 h post-load (P < 0.01) insulin levels, carotid IMT (P < 0.001), lower insulin-stimulated glucose disposal (P < 0.001), Matsuda index (P < 0.01), disposition index (P < 0.01), and insulin clearance (P < 0.001) as compared with subjects in the lowest tertile of circulating irisin levels. Irisin is inversely associated with insulin sensitivity and positively associated with carotid IMT in humans, suggesting either increased release by adipose/muscle tissue in response to deterioration of insulin sensitivity or a compensatory increase in irisin to overcome an underlying irisin resistance.
Relationship between circulating irisin, renal function and body composition in type 2 diabetes.
Liu Jian-Jun,Liu Sylvia,Wong Melvin D S,Tan Clara S H,Tavintharan Subramaniam,Sum Chee Fang,Lim Su Chi
Journal of diabetes and its complications
AIMS:Chronic kidney disease (CKD) secondary to type 2 diabetes mellitus (T2DM) is associated with multifaceted energy dysmetabolism. We aim to study the relationship between renal function, body composition and irisin, the recently identified myokine which is involved in energy regulation, in T2DM. METHODS:Circulating irisin and body composition were measured in 365 T2DM subjects across a wide range of renal function. RESULTS:Circulating irisin was significantly decreased in T2DM with renal insufficiency (77.4 ± 13.7 ng/ml in T2DM with eGFR ≥ 60 ml/min/1.73 m(2) versus 72.5 ± 14.9 ng/ml in those with eGFR<60 ml/min/1.73 m(2), p = 0.001) and the reduction in irisin was most pronounced in stage 5 CKD patients. In T2DM with preserved renal function, irisin was correlated with age (r = -0.242, p = 0.001) and pulse pressure (r = -0.188, p = 0.002). Among those with renal insufficiency, irisin was correlated with BMI (r = 0.171, p = 0.022), fat mass (r = 0.191, p = 0.013), percentage of fat mass (r = 0.210, p = 0.007) and eGFR (r = 0.171, p = 0.020). Multivariate linear regression models revealed that variations in circulating irisin were mainly attributable to eGFR and age in T2DM with and without renal impairment, respectively. CONCLUSION:Our observations suggest that the level of circulating irisin may be associated with renal function in T2DM. The role of reduced irisin in energy dysmetabolism in diabetic patients with renal insufficiency deserves further investigation.
Elevated circulating levels of irisin and the effect of metformin treatment in women with polycystic ovary syndrome.
Li Minyan,Yang Mengliu,Zhou Xiaoxin,Fang Xia,Hu Wenjing,Zhu Wei,Wang Cong,Liu Dongfang,Li Shengbing,Liu Hua,Yang Gangyi,Li Ling
The Journal of clinical endocrinology and metabolism
CONTEXT:Polycystic ovary syndrome (PCOS) is an insulin resistance (IR) state, like obesity and type 2 diabetes mellitus (T2DM). Although previous studies have suggested a correlation between irisin and the metabolic parameters associated with obesity and T2DM, the results have been inconsistent. OBJECTIVE:Our objective was to (1) determine circulating irisin levels in women with PCOS and control subjects, (2) examine the relationship of irisin and conventional markers of insulin resistance, and (3) examine irisin changes with interventions modulating IR in PCOS women. PATIENTS AND DESIGN:This study was comprised of a series of cross-sectional and interventional studies of 178 PCOS and 123 healthy women from the general population and outpatients of the Internal Medicine Department at the Second Affiliated Hospital, Chongqing Medical University, China. Forty seven women with PCOS were randomly assigned to 6 months of oral metformin (850 mg bid). The oral glucose tolerance test (OGTT) and the euglycemic-hyperinsulinemic clamp (EHC) were performed to assess glucose tolerance and insulin sensitivity. Outcome measures were IR (AUC(Insulin) and M values) on an OGTT and EHC, irisin levels, and metabolic markers. RESULTS:Circulating irisin was significantly higher in both overweight/obese (body mass index [BMI] ≥ 25 kg/m(2)) and PCOS women (P < .01). Circulating irisin levels correlated with BMI, WHR, FAT%, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), AUC(Insulin), homeostasis model assessment of insulin resistance (HOMA2-IR), M values, and free androgen index (FAI). During EHC, short-term hyperinsulinemia exhibited an inhibitory effect on irisin levels. After 6 months of metformin treatment, there was a significant decrease in circulating irisin in PCOS women following improved IR. CONCLUSIONS:These data suggest that irisin may be a useful marker of IR in PCOS women.
Superiority of the Non-Glycosylated Form Over the Glycosylated Form of Irisin in the Attenuation of Adipocytic Meta-Inflammation: A Potential Factor in the Fight Against Insulin Resistance.
Mazur-Bialy Agnieszka Irena
Irisin is an adipomyokine that promotes the browning of white adipose tissue and exhibits protective potential against the development of insulin resistance and type 2 diabetes. In our bodies, it occurs in its glycosylated form (G-IR): its activity is still poorly understood, because the majority of studies have used its non-glycosylated counterpart (nG-IR). Glycosylation can affect protein function: therefore, the present study attempted to compare the actions of both forms of irisin toward inflammatory activation of the main component of adipose tissue. The study was carried out in a coculture of 3T3 adipocytes and RAW 264.7 macrophages maintained in the presence of nG-IR or G-IR. The impact on vitality and the expression and release of key inflammatory mediators important for insulin resistance and diabetes development were assessed. The studies showed that both forms effectively inhibited the expression and release of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, macrophage chemotactic protein (MCP)-1, high-mobility group box (HMGB1), leptin, and adiponectin. However, in the case of TNF-α, IL-1β, MCP-1, and HMGB1, the inhibition exerted by nG-IR was more prominent than that by G-IR. In addition, only nG-IR significantly inhibited macrophage migration. Here, nG-IR seemed to be the stronger inhibitor of the development of obesity-related inflammation; however, G-IR also had anti-inflammatory potential.
Circulating irisin levels are positively associated with endothelium-dependent vasodilation in newly diagnosed type 2 diabetic patients without clinical angiopathy.
Xiang Lin,Xiang Guangda,Yue Ling,Zhang Junxia,Zhao Linshuang
OBJECTIVE:Irisin is a newly identified myokine that can promote energy expenditure and alleviate insulin-resistance in animal model. It has been established that insulin resistance is frequently associated with endothelial dysfunction. Therefore, we hypothesize that circulating irisin levels are associated with endothelial dysfunction in type 2 diabetes. METHODS:One hundred and eighty eight patients with newly diagnosed type 2 diabetes and 40 healthy subjects were recruited. Serum irisin concentrations were measured by using enzyme-linked immunosorbent assay, and flow-mediated dilation (FMD) was evaluated by using high-resolution ultrasound. RESULTS:The mean value of circulating irisin levels in newly diagnosed type 2 diabetes was 13.25 ng/ml, which was significantly lower than that in controls (25.98 ng/ml, p < 0.001). By dividing the distribution of FMD levels into quartiles, serum irisin levels were increased gradually with the increase of FMD levels (p < 0.001). Multivariate stepwise regression analysis demonstrated that serum irisin levels were independently associated with FMD (p = 0.009). By logistic regression analysis the odds ratio for lower FMD levels was reduced by 11.8% per 1 ng/ml increase in serum irisin concentration after adjustment for multivariate metabolic factors [OR (95% CI); 0.882 (0.709-0.969)]. CONCLUSION:These results demonstrated that circulating irisin levels were decreased in newly diagnosed Chinese type 2 diabetic patients without clinical angiopathy and positively associated with FMD levels.
Associations of betatrophin levels with irisin in Chinese women with normal glucose tolerance.
Xie Xinmiao,Gao Ting,Yang Meili,Chen Peihong,Jin Hua,Yang Lili,Yu Xuemei
Diabetology & metabolic syndrome
BACKGROUND:Betatrophin may increase islet β cell proliferation in insulin resistance and irisin may improve glucose tolerance in mice. To examine the relationship between betatrophin and irisin, we investigated it in middle-aged Chinese subjects with normal glucose tolerance (NGT) and type 2 diabetes mellitus (T2DM). METHODS:A total of 460 permanent residents of Fengxian District, aged 40-60 years and without T2DM, were enrolled. Anthropometric parameters, oral glucose tolerance test (OGTT) results, glycosylated haemoglobin levels, blood lipid levels, insulin sensitivity (homeostasis model assessment of insulin resistance, HOMA-IR), β cell function (homeostasis model assessment-β, HOMA-β), estimated glomerular filtration rate (eGFR) and body fat composition were determined. Matched for age, gender and body mass index (BMI, 18-28 kg/m2), newly diagnosed T2DM (n = 50, male/female = 23/27) and NGT (n = 50, male/female = 21/29) subjects were selected based on the results of an OGTT. Serum betatrophin and irisin levels were determined by enzyme linked immune sorbent assay (ELISA). RESULTS:Males had higher levels of betatrophin compared with females in both the NGT and T2DM groups. Compared with NGT subjects, the level of betatrophin in the T2DM group was higher, and males in the T2DM group had higher betatrophin levels than males in the NGT group, but there was no significant difference in betatrophin levels in females between the T2DM and NGT groups. Spearman's correlation analysis revealed that serum betatrophin levels in females with NGT were positively correlated with irisin and negatively correlated with FINS (fasting insulin) levels ( p < 0.05), but no correlation was found between betatrophin and irisin levels in males with NGT or in males or females with T2DM. In females with T2DM, circulating betatrophin levels were positively correlated with weight, BMI and hip circumference (p < 0.05) but negatively correlated with FPG (fasting plasma glucose) and HOMA-IR (p < 0.05). CONCLUSIONS:Gender differences in the relationship between betatrophin and irisin indicate that there might be cytokine-mediated crosstalk among the liver, adipose tissue and skeletal muscle.
Irisin Increased the Number and Improved the Function of Endothelial Progenitor Cells in Diabetes Mellitus Mice.
Zhu Guangxu,Wang Jinxiang,Song Mingbao,Zhou Fang,Fu Dagan,Ruan Guangping,Zhu Xiangqing,Bai Yinyin,Huang Lan,Pang Rongqing,Kang Huali,Pan Xinghua
Journal of cardiovascular pharmacology
The dysfunction of endothelial progenitor cells (EPCs) was found to be associated with vascular complications in diabetes mellitus (DM) patients. Previous studies found that regular exercise could improve the function of EPCs in DM patients, but the underling mechanism was unclear. Irisin, a newly identified myokine, was induced by exercise and has been demonstrated to mediate some of the positive effects of exercise. In this study, we hypothesize that irisin may have direct effects on EPC function in DM mice. These data showed for the first time that irisin increased the number of EPCs in peripheral blood of DM mice and improved the function of EPCs derived from DM mice bone marrow. The mechanism for the effect of irisin is related to the PI3K/Akt/eNOS pathway. Furthermore, irisin was demonstrated to improve endothelial repair in DM mice that received EPC transplants after carotid artery injury. The results of this study indicate a novel effect of irisin in regulating the number and function of EPCs via the PI3K/Akt/eNOS pathway, suggesting a potential for the administration of exogenous irisin as a succedaneum to improve EPC function in diabetic patients who fail to achieve such improvements through regular exercise.
Serum irisin concentration in women with gestational diabetes.
Kuzmicki Mariusz,Telejko Beata,Lipinska Danuta,Pliszka Justyna,Szamatowicz Michal,Wilk Juliusz,Zbucka-Kretowska Monika,Laudanski Piotr,Kretowski Adam,Gorska Maria,Szamatowicz Jacek
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
Irisin is a novel myokine and adipokine which induces an increase in total body energy expenditure, improving insulin sensitivity and glucose tolerance in experimental animals. In the present study, serum irisin concentration was measured by an enzyme immunoassay in 130 women with gestational diabetes mellitus (GDM) and 140 BMI-matched patients with normal glucose tolerance (NGT). Median irisin level was significantly lower in the patients with GDM than in the NGT subjects (1703.3 [1354.8-2097.9 ng/ml] versus 1873.8 [1519.8-2294.8 ng/ml], p = 0.01); however, 3 months after childbirth its concentrations did not differ markedly between the two groups (1165.9 [872.1-1497.5] ng/ml versus 1139.0 [984.0-1376.7] ng/ml). In the whole group, irisin concentration correlated negatively with 2 h glucose level (R = -0.14, p = 0.03). In the women with NGT, irisin concentration correlated positively with IS(OGTT) (R = 0.22, p = 0.04) and the disposition index (DI(120)) (R = 0.24, p = 0.03), as well as negatively with 2 h insulin level (R = -0.23, p = 0.03) and HOMA-IR (R = -0.24, p = 0.02). Multiple regression analysis revealed that 2 h glucose and DI(120) were the only variables significantly influencing serum irisin (β = 0.158, p = 0.03 and β = 0.159, p = 0.02, respectively). Our results suggest that serum irisin concentration increases markedly in pregnant women, but this increase seems to be significantly lower in patients with GDM.
Circulating levels of irisin in middle-aged first-degree relatives of type 2 diabetes mellitus - correlation with pancreatic β-cell function.
Yang Meili,Chen Peihong,Jin Hua,Xie Xinmiao,Gao Ting,Yang Lili,Yu Xuemei
Diabetology & metabolic syndrome
BACKGROUND:Irisin is a novel myokine secreted in response to peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) activation through exercise. The first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM) patients bear a lifetime risk for developing T2DM, especially after 40 years old. However, the circulating irisin levels in middle-aged FDRs of T2DM is unclear. We therefore investigated the association between circulating irisin and pancreatic β-cell function in normal-glucose-tolerance (NGT) subjects. METHODS:In this cross-sectional study, we recruited 412 supposed healthy subjects aged 40-60 who were FDRs of T2DM patients but without previous diagnosis of T2DM. Of the 412 individuals, 254 had NGT and 60 were newly diagnosed T2DM based on the results of a 75 g oral glucose tolerance test (OGTT- World Health Organization diagnostic criteria). We measured irisin in the newly diagnosed T2DM group (n = 60) and in an age- and sex-matched NGT subgroups (n = 62). Serum irisin was quantified by ELISA, and its association with metabolic parameters was analysed by Pearson's correlation and multiple linear regression analyses. RESULTS:There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients and the NGT control group. Circulating irisin was correlated with haemoglobin A1c (r = 0.202, p = 0.026) and estimated glomerular filtration rate (r = 0.239, p = 0.010). Multiple linear regression revealed that only homeostasis model assessment-β (HOMA-β) was associated with irisin in NGT subjects after adjusting for confounding factors. However, similar analysis in T2DM did not reveal a significant association between circulating irisin and metabolic parameters. CONCLUSIONS:There was no significant difference in serum irisin between middle-aged newly diagnosed T2DM patients and the NGT controls. Serum irisin level was closely related to HOMA-β in NGT, suggesting that irisin may play a crucial role in pancreatic β-cell function.
Association between irisin and homocysteine in euglycemic and diabetic subjects.
Alis Rafael,Sanchis-Gomar Fabian,Pareja-Galeano Helios,Hernández-Mijares Antonio,Romagnoli Marco,Víctor Víctor M,Rocha Milagros
OBJECTIVES:The aim of study was to explore whether a relationship exists between homocysteine and irisin in type 2 diabetes (T2D) patients-a population with a high risk of developing cardiovascular disease-and euglycemic controls. DESIGN AND METHODS:69 T2D patients and 75 control subjects (adjusted by body mass index (BMI)) were included in the study. Irisin and homocysteine concentrations and anthropometric and biochemical variables were determined. RESULTS:Levels of homocysteine were significantly higher (11.0±3.0 vs 12.4±4.2 μmol/l) and levels of irisin were lower (279±58 vs 263±38 ng/ml) in T2D patients. When both T2D and controls were considered, irisin was found to correlate only with homocysteine (r=-0.215; p=0.011). Moreover, a decreasing trend in irisin levels was observed according to homocysteine tertile (p=0.034). CONCLUSIONS:Our results provide evidence of an association between irisin and homocysteine, which may be due to nicotinamide metabolism. The clinical significance of this relationship is unclear, but our findings may prompt further mechanistic research to investigate the role played by irisin in vascular disorders.
Increased levels of irisin in people with long-standing Type 1 diabetes.
Espes D,Lau J,Carlsson P O
Diabetic medicine : a journal of the British Diabetic Association
BACKGROUND:Irisin stimulates browning of white adipose tissue and improves metabolic control in mice. Betatrophin, another recently described hormone, improves metabolic control in mice by inducing β-cell proliferation. In vitro, irisin stimulates the expression of betatrophin in rat adipocytes. There is a great interest in developing drugs that target or use these hormones for the treatment of obesity and diabetes. We have previously reported on increased levels of betatrophin in people with Type 1 diabetes, but the levels of irisin are currently unknown. AIM:To characterize the levels of irisin in Type 1 diabetes and investigate a potential correlation with betatrophin. METHODS:Irisin and betatrophin were measured by enzyme-linked immunosorbant assay (ELISA) in 45 individuals with Type 1 diabetes and in 25 healthy controls. RESULTS:Irisin levels were increased in people with Type 1 diabetes, and especially in women. Negative correlations between irisin levels and age at onset of Type 1 diabetes and plasma triacylglycerol levels were observed. Interestingly, in women with Type 1 diabetes a negative correlation between irisin and insulin doses was also observed. When computing correlations for all study participants, a positive correlation between irisin and total betatrophin was observed, but not between irisin and full-length betatrophin. CONCLUSION:We report on increased circulating levels of irisin in people with Type 1 diabetes, especially in women. For women with Type 1 diabetes, the levels of irisin correlated with lower insulin requirements. Further studies are clearly needed to determine the role of irisin in Type 1 diabetes.
Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk.
Bonfante Ivan Luiz Padilha,Chacon-Mikahil Mara Patricia Traina,Brunelli Diego Trevisan,Gáspari Arthur Fernandes,Duft Renata Garbellini,Oliveira Alexandre Gabarra,Araujo Tiago Gomes,Saad Mario Jose Abdalla,Cavaglieri Cláudia Regina
Archives of endocrinology and metabolism
OBJECTIVE:Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. SUBJECTS AND METHODS:On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. RESULTS:The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p < 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r -0.46, p = 0.04), neck circumference (r -0.51, p = 0.02), free fat mass (r -0.49, p = 0.02), triglycerides (r -0.43, p = 0.05) and risk of developing T2DM (r -0.61, p = 0.04) were observed. CONCLUSIONS:These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance.
Role of serum levels of irisin and oxidative stress markers in pregnant women with and without gestational diabetes.
Usluoğullari Betül,Usluogullari Celil Alper,Balkan Fevzi,Orkmez Mustafa
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
Irisin regulates glucose levels, lipid levels, insulin sensitivity, and low-grade inflammation. Gestational diabetes mellitus (GDM) is a common metabolic complication of pregnancy, and is associated with increased rates of perinatal problems. Oxidative stress biomarkers have a role in the pathogenesis of patients with GDM. In total, 94 patients were included in our study including 46 control patients and 48 patients with GDM. Fasting blood glucose, HOMA-IR, total oxidative stress (TOS), irisin, and oxidative stress index (OSI) levels of the patients were measured. Serum OGTT, OSI, irisin HOMA, TOS, and insulin levels were statistically significantly higher in the patient group than in the control group. This was the first study to investigate the relation between serum irisin levels and oxidative stress markers in patients with GDM. The results revealed that irisin is an oxidative stress marker and a metabolic protective hormone.
Irisin levels are associated with urotensin II levels in diabetic patients.
He Wan-Yu,Bai Qiong,A La-Ta,Tang Chao-Shu,Zhang Ai-Hua
Journal of diabetes investigation
AIMS/INTRODUCTION:Irisin is a newly identified myokine that can promote energy expenditure. Previous studies showed that circulating urotensin II (UII) levels were increased in diabetes, and UII could inhibit the glucose transport in skeletal muscle in diabetic mice and aggravated insulin resistance. We presumed that irisin levels are associated with UII in diabetic patients. MATERIALS AND METHODS:A total of 71 patients with type 2 diabetes and 40 healthy subjects were recruited. Blood and urinary irisin concentrations were measured by using enzyme-linked immunosorbent assay, and UII concentrations were measured by bioelectrical impedance analysis. Every participant's body composition was analyzed by bioelectrical impedance. RESULTS:The serum irisin levels were significantly lower in diabetic patients than that of controls, whereas serum UII levels were significantly higher in diabetic patients than that in that of controls. Serum irisin levels were negatively associated with circulating UII, hemoglobin A1c and the natural logarithm transformation of urinary albumin excretion, whereas serum irisin was positively associated with estimated glomerular filtration rate, and low-density lipoprotein cholesterol and urinary irisin were positively associated with urinary UII. Furthermore, circulating irisin is positively associated with muscle mass, whereas circulating UII is negatively associated with muscle mass in diabetic patients. Hemoglobin A1c and circulating UII are independent determinants of circulating irisin by multiple regression analysis. CONCLUSIONS:The present results provide the clinical evidence of an association between irisin and UII in diabetic patients. Hemoglobin A1c and circulating UII are independent determinants of circulating irisin. Our results hint that UII and high glucose might inhibit the release of irisin from skeletal muscle in diabetic patients.
Irisin ameliorates hepatic glucose/lipid metabolism and enhances cell survival in insulin-resistant human HepG2 cells through adenosine monophosphate-activated protein kinase signaling.
So Wing Yan,Leung Po Sing
The international journal of biochemistry & cell biology
Irisin is a newly identified myokine that promotes the browning of white adipose tissue, enhances glucose uptake in skeletal muscle and modulates hepatic metabolism. However, the signaling pathways involved in the effects on hepatic glucose and lipid metabolism have not been resolved. This study aimed to examine the role of irisin in the regulation of hepatic glucose/lipid metabolism and cell survival, and whether adenosine monophosphate-activated protein kinase (AMPK), a master metabolic regulator in the liver, is involved in irisin's actions. Human liver-derived HepG2 cells were cultured in normal glucose-normal insulin (NGNI) or high glucose-high insulin (HGHI/insulin-resistant) condition. Hepatic glucose and lipid metabolism was evaluated by glucose output and glycogen content or triglyceride accumulation assays, respectively. Our results showed that irisin stimulated phosphorylation of AMPK and acetyl-CoA-carboxylase (ACC) via liver kinase B1 (LKB1) rather than Ca(2+)/calmodulin-dependent protein kinase kinase β (CaMKKβ) in HepG2 cells. Irisin ameliorated hepatic insulin resistance induced by HGHI condition. Irisin reduced hepatic triglyceride content and glucose output, but increased glycogen content, with those effects reversed by dorsomorphin, an AMPK inhibitor. Furthermore, irisin also stimulated extracellular signal-regulated kinase (ERK) 1/2 phosphorylation and promoted cell survival in an AMPK-dependent manner. In conclusion, our data indicate that irisin ameliorates dysregulation of hepatic glucose/lipid metabolism and cell death in insulin-resistant states via AMPK activation. These findings reveal a novel irisin-mediated protective mechanism in hepatic metabolism which provides a scientific basis for irisin as a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes mellitus.
Irisin levels in the progression of diabetes in sedentary women.
Duran Iffet Dağdelen,Gülçelik Neşe Ersöz,Ünal Mustafa,Topçuoğlu Canan,Sezer Sevilay,Tuna Mazhar Müslüm,Berker Dilek,Güler Serdar
CONTEXT:The recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. However, studies ended up with controversial results. In the present study, we aimed to investigate irisin levels in sedentary women at different stages of prediabetes. DESIGN, SETTING, AND SUBJECTS:We performed a cross-sectional analysis of circulating levels of irisin in 263 females similar for age and body mass index (BMI) and the groups included 52 normal glucose tolerance (NGT), 60 isolated impaired fasting glucose (IFG), 36 isolated impaired glucose tolerance (IGT), 65 both IFG and IGT and 50 type 2 diabetic patients. All patients were exercising less than 150 min/week. RESULTS:Plasma irisin levels were significantly lower in IFG+IGT (2.86 ± 0.6 μg/mL, p: 0.019) and T2DM (2.83 ± 0,5 μg/mL, p: 0.005) patients compared to NGT (3.16 ± 0.3 μg/mL) patients. After age adjustment there was a negative correlation between irisin and BMI (r: -0.141; p: 0.031), postprandial glucose (PPG) (r: -0.142; p: 0.030), low density lipoprotein-cholesterol (LDL-C) (r: -0.138; p: 0.035) and triglyceride (TG) (r: -0.214; p: 0.001) and a positive correlation between irisin and high density lipoprotein-cholesterol (HDL-C) (r:.142; p: 0.030). After adjustment for age and BMI; PPG (r: -0. 137; p: 0.037), LDL-C (r: -0. 143; p: 0.029) and TG (r: -0.203; p: 0.002) were considered to correlate with irisin levels. Subgroup analysis revealed that TG levels were correlated with irisin levels in IFG (r: -0.347; p: 0.014) and IGT (r: -0.397; p: 0.030) patients. CONCLUSION:In our cohort of sedentary women, irisin levels were lower in patients with IFG+IGT and with diabetes than in patients with NGT. There is no correlation between irisin levels and BMI. Irisin is a myokine decreasing gradually with the progression of glucose intolerance and T2DM and is not correlated with BMI in sedentary women.
Irisin protects against endothelial injury and ameliorates atherosclerosis in apolipoprotein E-Null diabetic mice.
Lu Junyan,Xiang Guangda,Liu Min,Mei Wen,Xiang Lin,Dong Jing
OBJECTIVE:The circulating irisin increases energy expenditure and improves insulin resistance in mice and humans. The improvement of insulin resistance ameliorates atherosclerosis. Therefore, we hypothesized that irisin alleviates atherosclerosis in diabetes. METHODS:Endothelial function was measured by acetylcholine-induced endothelium-dependent vasodilation using aortic rings in apolipoprotein E-Null (apoE(-/-)) streptozotocin-induced diabetic mice. Atherosclerotic lesion was evaluated by plaque area and inflammatory response in aortas. In addition, the endothelium-protective effects of irisin were also further investigated in primary human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS:The in vivo experiments showed that irisin treatment significantly improved endothelial dysfunction, decreased endothelial apoptosis, and predominantly decreased atherosclerotic plaque area of both en face and cross sections when compared with normal saline-treated diabetic mice. Moreover, the infiltrating macrophages and T lymphocytes within plaque and the mRNA expression levels of inflammatory cytokines in aortas were also significantly reduced by irisin treatment in mice. The in vitro experiments revealed that irisin inhibited high glucose-induced apoptosis, oxidative stress and increased antioxidant enzymes expression in HUVECs, and pretreatment with LY294002, l-NAME, AMPK-siRNA or eNOS-siRNA, attenuated the protection of irisin on HUVECs apoptosis induced by high glucose. In addition, the in vivo and in vitro experiments showed that irisin increased the phosphorylation of AMPK, Akt and eNOS in aortas and cultured HUVECs. CONCLUSIONS:The present study indicates that systemic administration of irisin may be protected against endothelial injury and ameliorated atherosclerosis in apoE(-/-) diabetic mice. The endothelium-protective action of irisin was through activation of AMPK-PI3K-Akt-eNOS signaling pathway. Irisin could be therapeutic for atherosclerotic vascular diseases in diabetes.
Serum sclerostin and irisin as predictive markers for atherosclerosis in Egyptian type II diabetic female patients: A case control study.
Saadeldin Mona Kamal,Elshaer Shereen Saeid,Emara Ibrahim Ali,Maged Mohamad,Abdel-Aziz Amal Kamal
Diabetes mellitus represents a major independent risk factor for developing fatal cardiovascular diseases (CVDs) presumably through accelerating atherosclerosis; the underlying cause of most CVDs. Notably, this relative risk is reported to be higher in women than men. Endeavors directed towards identifying novel reliable predictive biomarkers are immensely thereby urged to improve the long-term outcome in these diabetic female patients. Sclerostin (SOST) is a Wnt signaling antagonist whereas irisin is a muscle-derived factor released after exercising which enhances browning of white adipose tissue. Emerging lines of evidence hint at potential crosstalk between them and CVDs. The present study aimed to assess the serum levels of SOST and irisin in Egyptian type 2 diabetic (T2DM) female patients with and without atherosclerosis and explore the possible relationship between both markers and other studied parameters among the studied cohorts. In this case-control study, 69 female subjects were enrolled; 39 type 2 diabetes patients with atherosclerosis (T2DM+ATHR), 22 type 2 diabetes patients without atherosclerosis (T2DM-ATHR) and 8 healthy controls. Their serum levels of SOST and irisin were assessed using ELISA. Significant increase in SOST levels were found in T2DM+ATHR compared to T2DM-ATHR and control (259.9 ±17.98 vs. 165.8±13.12 and 142.0±13.31 pg/mL respectively, P<0.001). Conversely, irisin levels were significantly lower in T2DM+ATHR (P<0.001) and T2DM-ATHR (P<0.01) compared to the control group (32.91±2.545 and 58.55±13.19 vs. 473.6±112.7 pg/mL). Interestingly, significant correlations between the levels of SOST and both irisin and fasting blood glucose were noticed in T2DM+ATHR group (r = 0.3754 and 0.3381 respectively, P<0.05). In conclusion, to the best of our knowledge, this study is the first to demonstrate the correlation between SOST and irisin levels in atherosclerotic T2DM female patients implying their potential implication in diabetic cardiovascular pathophysiology and supporting their use as reliable diagnostic/prognostic biomarkers for monitoring and preventing CVDs progression of T2DM female patients.
Alteration of maternal serum irisin levels in gestational diabetes mellitus.
Ural Ulku Mete,Sahin Serap Baydur,Tekin Yesim Bayoglu,Cüre Medine Cumhur,Sezgin Hacer
OBJECTIVES:The aim of our study was to compare serum irisin concentrations in pregnant women with and without ges-tational diabetes mellitus (GDM). MATERIAL AND METHODS:This study was performed at the Tertiary Care Center, Department of Obstetrics and Gynecol-ogy, between January 2014 and April 2014. A total of 45 pregnant women with GDM (diabetes group) and 41 BMI- and age-matched healthy pregnant women (control group) were recruited. Maternal serum irisin levels were measured by enzyme-linked immunosorbent assay kit at 24-28 weeks of gestation. An association between maternal serum irisin lev-els and metabolic parameters was analyzed. Body mass index, serum levels of glucose, insulin and irisin were tested and analyzed in the study group and controls. RESULTS:Pregnant women with GDM had significantly higher fasting plasma glucose (p = 0.001), first-hour OGTT glucose (p = 0.001), second-hour OGTT glucose (p = 0.001), and fasting insulin (p = 0.045) levels as compared to controls. Serum irisin levels were 1.04 ± 0.3 and 1.3 ± 0.2 in pregnant women with GDM and healthy pregnant controls, respectively (p = 0.001). Correlation analysis between irisin levels and anthropometric and biochemical parameters in patients with gestational diabetes revealed that none of the investigated parameters correlated with serum irisin level. CONCLUSIONS:Our results suggest that serum irisin levels might be introduced as a novel marker for GDM, with decreased levels of irisin being indicative of GDM.
Circulating irisin levels are associated with lipid and uric acid metabolism in a Chinese population.
Tang Shanshan,Zhang Rong,Jiang Feng,Wang Jie,Chen Miao,Peng Danfeng,Yan Jing,Wang Shiyun,Bao Yuqian,Hu Cheng,Jia Weiping
Clinical and experimental pharmacology & physiology
Irisin is a novel hormone secreted by skeletal muscle after exercise, which may ameliorate insulin resistance. In this study, we aimed to explore the relationship between circulating irisin levels and type 2 diabetes mellitus (T2DM) as well as related metabolic traits in a Chinese population. A total of 203 subjects were recruited. Of these, 68 subjects with normal glucose tolerance (NGT), 63 subjects with impaired glucose regulation (IGR) and 72 subjects with new-onset T2DM. Circulating irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Detailed clinical investigations and biochemistry measurements were carried out in all of the subjects. Multivariate linear regression analysis was performed to assess the association between irisin levels and related metabolic characteristics. All subjects were classified into normal weight and overweight/obese subgroups according to body mass index (BMI). No significant differences in circulating irisin levels were identified among the three groups (P = 0.9741). After adjusting for covariates, multiple linear regression analysis revealed that serum irisin level was independently and significantly associated with total cholesterol (P = 0.0005), low-density lipoprotein cholesterol (P = 0.0014), fasting fatty acids (P = 0.0402) and uric acid (P = 0.0062). By dividing the serum irisin levels into three tertile groups, the values of total cholesterol, low-density lipoprotein cholesterol, fasting fatty acids and uric acid were all increased significantly with the increase of irisin (P < 0.05). Moreover, serum irisin levels remain closely related to total cholesterol in both normal weight and overweight/obese subgroups. Our study suggests that circulating irisin concentrations are significantly associated with lipid and uric acid metabolism in a Chinese population.
Factors associated with increased irisin levels in the type 1 diabetes mellitus.
Ates I,Arikan M F,Erdogan K,Kaplan M,Yuksel M,Topcuoglu C,Yilmaz N,Guler S
OBJECTIVE:The aim of the present study was to determine the irisin levels in patients with the type 1 diabetes mellitus (T1DM) and to examine the relation of irisin levels with the inflammation and autoimmunity. METHODS:This study included 35 cases diagnosed with T1DM and 36 healthy volunteers. Antiglutamic acid decarboxylase (anti-GAD), islet cell antibody (ICA), and insulin autoantibody levels were measured in patients at the time when they were included into the study and recorded from the patient files. Serum irisin levels were measured by ELISA kit. RESULTS:The median irisin levels were determined higher in T1DM group compared to the control one (6.8 ng/ml vs. 4.8 ng/ml, p=0.022; respectively). Median irisin levels were higher in anti-GAD (p=0.022) and ICA (p=0.044) positive groups compared to negative groups. In T1DM group, irisin levels displayed positive correlation with glycosylated hemoglobin (HbA1c) (r=0.377, p<0.001) and anti-GAD (r=0.392, p=0.020) and negative correlation with creatinine (r=-0390, p=0.021). In multivariate regression model, HbA1c (B±SE: 2.76±17683, p<0.001), and anti-GAD (B±SE: 2.311±0.610, p=0.001) were determined as independent predictors for predicting the irisin levels. CONCLUSION:In patients with T1DM, which chronic inflammation and autoimmunity take part in their etiopathogenesis, anti-GAD levels were an independent risk factor for the irisin. Th is may suggest that factors such as inflammation and autoimmunity can be effective in the synthesis of irisin.
Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses.
Zhu Di,Wang Haichang,Zhang Jinglong,Zhang Xiaotian,Xin Chao,Zhang Fuyang,Lee Yan,Zhang Ling,Lian Kun,Yan Wenjun,Ma Xinliang,Liu Yi,Tao Ling
Journal of molecular and cellular cardiology
Vascular complications are the major causes of death in patients with diabetes, and endothelial dysfunction is the earliest event in vascular complications of diabetes. It has been reported that plasma irisin level is significantly reduced in patients with type 2 diabetic patients. The present study aimed to investigate whether irisin improved endothelial function in type 2 diabetes as well as the underlying mechanisms. The type 2 diabetes model was established by feeding C57BL/6 mice with high-fat diet. The type 2 diabetic mice exhibited reduced serum irisin level and impaired endothelial function. Irisin treatment (0.5 mg/kg/d) for two weeks improved vascular function based on the evaluation of endothelium-dependent vasorelaxation and p-VASP levels. To investigate the direct endothelial protective effects of irisin, diabetic aortic segments were incubated with irisin (1 μg/ml) ex vivo. Exposure to irisin improved endothelium-dependent vasorelaxation of diabetic aortas. Mechanically, the diabetic aortic segments exhibited increased oxidative/nitrative stresses. Irisin reduced the diabetes-induced oxidative/nitrative stresses evidenced by reducing overproduction of superoxide and peroxynitrite, and down-regulation of iNOS and gp91(phox). To further investigate the protective effects of irisin on endothelial cells and the underlying mechanisms, human umbilical vein endothelial cells (HUVECs) cultured in high-glucose/high-fat (HG/HF) medium were pre-incubated with irisin. Irisin (1 μg/ml) reduced the oxidative/nitrative stresses and apoptosis induced by HG/HF in HUVECs probably via inhibiting activation of PKC-β/NADPH oxidase and NF-κB/iNOS pathways. Taken together, irisin alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses through inhibiting signaling pathways implicating PKC-β/NADPH oxidase and NF-κB/iNOS, suggesting that irisin may be a promising molecule for the treatment of vascular complications of diabetes.
Anti-diabetic activity of recombinant irisin in STZ-induced insulin-deficient diabetic mice.
Duan Huikun,Ma Baicheng,Ma Xiaofeng,Wang Haisong,Ni Zaizhong,Wang Bin,Li Xiaodan,Jiang Pingzhe,Umar Muhammad,Li Minggang
International journal of biological macromolecules
In order to investigate the hypoglycemic effects and potential mechanism of recombinant irisin on diabetes, STZ-induced diabetic mice were established and treated with irisin. The results showed that daily water and food intake, and blood glucose significantly decreased after various concentrations of recombinant irisin treatment by intraperitoneal injection, of which 1.0 mg/kg was the optimal dose for lowering blood glucose. However, the body weight exhibited no significant difference during the treatment within groups, although the 0.9% NaCl treated group showed a trend of decreased body weight and the irisin treated groups showed a tendency of increasing weight. The oral glucose tolerance was improved, and serum insulin and circulating irisin content were significantly elevated in diabetic mice after 1.0 mg/kg irisin-injection treatment, compared to diabetic mice treated with 0.9% NaCl. 1.0 mg/kg irisin-injection also significantly increased the expression of energy and metabolism-related genes. In addition, oral administration of irisin lowered the blood glucose in diabetic mice. Our data suggested that irisin could lower blood glucose in insulin-deficient diabetic mice, to some extent, through irisin-mediated induction of energy and metabolic genes expression. These observations laid a foundation for the development of irisin-based therapy.
Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes.
Liu Tong-Yan,Shi Chang-Xiang,Gao Run,Sun Hai-Jian,Xiong Xiao-Qing,Ding Lei,Chen Qi,Li Yue-Hua,Wang Jue-Jin,Kang Yu-Ming,Zhu Guo-Qing
Clinical science (London, England : 1979)
Increased glucose production and reduced hepatic glycogen storage contribute to metabolic abnormalities in diabetes. Irisin, a newly identified myokine, induces the browning of white adipose tissue, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of irisin on gluconeogenesis and glycogenesis in hepatocytes with insulin resistance, and its therapeutic role in type 2 diabetic mice. Insulin resistance was induced by glucosamine (GlcN) or palmitate in human hepatocellular carcinoma (HepG2) cells and mouse primary hepatocytes. Type 2 diabetes was induced by streptozotocin/high-fat diet (STZ/HFD) in mice. In HepG2 cells, irisin ameliorated the GlcN-induced increases in glucose production, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression, and glycogen synthase (GS) phosphorylation; it prevented GlcN-induced decreases in glycogen content and the phosphoinositide 3-kinase (PI3K) p110α subunit level, and the phosphorylation of Akt/protein kinase B, forkhead box transcription factor O1 (FOXO1) and glycogen synthase kinase-3 (GSK3). These effects of irisin were abolished by the inhibition of PI3K or Akt. The effects of irisin were confirmed in mouse primary hepatocytes with GlcN-induced insulin resistance and in human HepG2 cells with palmitate-induced insulin resistance. In diabetic mice, persistent subcutaneous perfusion of irisin improved the insulin sensitivity, reduced fasting blood glucose, increased GSK3 and Akt phosphorylation, glycogen content and irisin level, and suppressed GS phosphorylation and PEPCK and G6Pase expression in the liver. Irisin improves glucose homoeostasis by reducing gluconeogenesis via PI3K/Akt/FOXO1-mediated PEPCK and G6Pase down-regulation and increasing glycogenesis via PI3K/Akt/GSK3-mediated GS activation. Irisin may be regarded as a novel therapeutic strategy for insulin resistance and type 2 diabetes.
Association of irisin concentrations with the presence of diabetic nephropathy and retinopathy.
Hu Wenchao,Wang Rui,Li Jun,Zhang Jie,Wang Wenhui
Annals of clinical biochemistry
OBJECTIVE:Irisin, a recently identified myokine, is involved in the protection of mice against obesity and diabetes. This study aims to determine the serum and vitreous concentrations of irisin in patients with diabetic nephropathy and diabetic retinopathy. METHODS:A total of 178 patients with type 2 diabetes mellitus, as well as 22 type 2 diabetes mellitus patients without diabetic retinopathy and 35 patients with proliferative diabetic retinopathy were enrolled in this study. RESULTS:Serum irisin concentrations were significantly elevated in the control group compared with those in type 2 diabetes mellitus patients. Furthermore, type 2 diabetes mellitus patients with macroalbuminuria exhibited significantly lower serum irisin concentrations than the controls and type 2 diabetes mellitus patients with normoalbuminuria and microalbuminuria. Simple regression analysis showed that the serum irisin concentrations in type 2 diabetes mellitus patients were negatively correlated with age, fasting plasma glucose, homeostasis model assessment of insulin resistance, blood urea nitrogen, creatinine, and positively correlated with creatinine clearance and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers treatment. Proliferative diabetic retinopathy patients showed significantly decreased serum and vitreous irisin concentrations compared with the control group and type 2 diabetes mellitus patients without diabetic retinopathy. Furthermore, decreased serum and vitreous irisin concentrations were found in type 2 diabetes mellitus patients without diabetic retinopathy than those in the controls. CONCLUSION:Irisin concentrations are associated with the presence of diabetic nephropathy and diabetic retinopathy.
Exenatide treatment increases serum irisin levels in patients with obesity and newly diagnosed type 2 diabetes.
Liu Jia,Hu Yanjin,Zhang Heng,Xu Yuan,Wang Guang
Journal of diabetes and its complications
OBJECTIVE:Irisin is a myokine secreted by skeletal muscle during exercise. Abnormal serum irisin levels are associated with obesity and type 2 diabetes (T2D). This study investigated the changes in serum irisin in the obese patients with newly diagnosed T2D following glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide) treatment. METHODS:Fifty-four obese patients with T2D were treated with exenatide for 12weeks. The control group included 54 age-, sex-, and body mass index (BMI)-matched subjects with normal glucose tolerance. RESULTS:Patients with T2D had lower irisin than the control group (38.06 [29.29-53.79] vs. 58.01 [43.07-87.79] ng/mL, P<0.01]. Serum irisin was negatively associated with BMI (r=-0.178, P<0.05), fasting blood glucose (FBG; r=-0.170, P<0.05), and glycosylated hemoglobin (HbA1c; r=-0.189, P<0.01) in patients with T2D. Exenatide treatment markedly increased serum irisin by 19.28ng/mL (12.59-25.98) compared to baseline (P<0.01). Increased irisin was significantly correlated with decreased FBG and HbA1c after exenatide treatment (FBG: r=-0.35; HbA1c: r=-0.37; both P<0.05). CONCLUSIONS:Exenatide treatment significantly increased irisin in patients with T2D. Post-treatment changes in irisin were correlated with decreases in FBG and HbA1c. The upregulation of irisin might be a novel mechanism for the beneficial effects of exenatide in type 2 diabetic patients.
Relationship between myostatin and irisin in type 2 diabetes mellitus: a compensatory mechanism to an unfavourable metabolic state?
García-Fontana Beatriz,Reyes-García Rebeca,Morales-Santana Sonia,Ávila-Rubio Verónica,Muñoz-Garach Araceli,Rozas-Moreno Pedro,Muñoz-Torres Manuel
Myostatin and irisin are two myokines related to energy metabolism, acting on skeletal muscle and recently suggested on adipose tissue in mice. However, the exact role of these myokines in humans has not been fully established. Our aim was to evaluate the relationship between serum levels of myostatin and irisin in type 2 diabetes mellitus patients and non-diabetic controls and to explore its links with metabolic parameters. Case-control study including 73 type 2 diabetes mellitus patients and 55 non-diabetic subjects as control group. Circulating myostatin and irisin levels were measured by enzyme-linked immunosorbent assays. Type 2 diabetes mellitus patients showed significantly lower myostatin levels (p = 0.001) and higher irisin levels (p = 0.036) than controls. An inverse relationship was observed between myostatin and irisin levels (p = 0.002). Moreover, in type 2 diabetes mellitus patients, after adjusting by confounder factors, myostatin was negatively related to fasting plasma glucose (p = 0.005) and to triglyceride levels (p = 0.028) while irisin showed a positive association with these variables (p = 0.017 and p = 0.006 respectively). A linear regression analysis showed that irisin and fasting plasma glucose levels were independently associated to myostatin levels and that myostatin and triglyceride levels were independently associated to irisin concentrations in type 2 diabetes mellitus patients. Our results suggest that serum levels of myostatin and irisin are related in patients with type 2 diabetes. Triglyceride and glucose levels could modulate myostatin and irisin concentrations as a compensatory mechanism to improve the metabolic state in these patients although further studies are needed to elucidate whether the action of these myokines represents an adaptative response.
Effects and underlying mechanisms of irisin on the proliferation and apoptosis of pancreatic β cells.
Liu Shiwei,Du Fang,Li Xin,Wang Mingming,Duan Ruixue,Zhang Jiaxin,Wu Yaru,Zhang Qi
Pancreatic β cell dysfunction and reduction due to glucose toxicity play a crucial role in the development of type 2 diabetes mellitus (T2DM). Irisin, a novel exercise-induced myokine, reduces obesity, improves insulin resistance and lowers blood glucose by promoting the browning of white adipose tissue, thereby enhancing thermogenesis and increasing energy expenditure. Recent studies have reported that irisin promotes cell proliferation and protects cells from apoptosis. However, the effects of irisin on pancreatic β cells are unknown. Thus, the aim of this study was to investigate the effects and the potential underlying mechanisms of irisin on pancreatic β cell proliferation and apoptosis induced by high glucose. Both in vitro (INS-1 cells) and in vivo (a T2DM rat model) experiments were conducted. Irisin significantly increased the proliferation of INS-1 cells, with the most significant effect observed at 24 h with 100 ng/ml irisin. Irisin also promoted INS-1 cell proliferation via the ERK and p38 MAPK signaling pathways, protected the cells from high-glucose-induced apoptosis by regulating the expression of caspases, Bad, Bax, Bcl-2 and Bcl-xl, and improved pancreatic β cell function. Irisin significantly reduced the body weight and blood glucose values and increased the serum insulin levels of the diabetic rats. An oral glucose tolerance test (OGTT) indicated that irisin also improved the glucose tolerance of T2DM rats. Together, these findings suggest that irisin may have applications in the prevention and treatment of T2DM because of its protective effect on the secretion of pancreatic β cells.
Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults.
Shi Xiulin,Lin Mingzhu,Liu Changqin,Xiao Fangsen,Liu Yongwen,Huang Peiying,Zeng Xin,Yan Bing,Liu Suhuan,Li Xiaoying,Yang Shuyu,Li Xuejun,Li Zhibin
BMC endocrine disorders
BACKGROUND:Evidence on the role of irisin in insulin resistance is limited and controversial, and pathways between them remain unknown. We aimed to examine the independent effects of circulating irisin and different adiposity measurements, as well as their potential interactions, on insulin resistance. We also aimed to explore possible pathways among circulating irisin, adiposity, glucose and insulin levels and insulin resistance. METHODS:A cross-sectional study of 1,115 community- living obese Chinese adults, with data collection on clinical characteristics, glucose and lipid metabolic parameters and circulating irisin levels. RESULTS:Among the 1,115 subjects, 667 (59.8 %) were identified as insulin-resistance, and showed significantly decreased serum irisin than their controls (log-transformed irisin: 1.19 ± 2.34 v.s. 1.46 ± 2.05 ng/ml, p = 0.042). With adjustment for potential confounders, elevated circulating irisin was significantly associated with reduced risk of insulin resistance, with adjusted odds ratio per standard deviation increase of irisin of 0.871 (0.765-0.991, p = 0.036). As for different adiposity measurements, body fat percentage, but neither BMI nor waist, was significantly associated with increased risk of insulin resistance (OR: 1.152 (1.041-1.275), p = 0.006). No significant interaction effect between serum irisin and adiposity on insulin resistance was found. A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ (2) = 44.09, p < 0.001; CFI-0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = -0.046, p = 0.032). CONCLUSIONS:Elevated circulating irisin is associated with lower risk of insulin resistance indirectly through lowering fasting insulin.
Irisin modulates the association of interleukin-17A with the presence of non-proliferative diabetic retinopathy in patients with type 2 diabetes.
Wang Chuan,Wang Lingshu,Liu Jinbo,Song Jun,Sun Yu,Lin Peng,Liang Kai,Liu Fuqiang,He Tianyi,Sun Zheng,Hou Xinguo,Chen Li
The role of inflammation in pathogenesis of diabetic retinopathy (DR) is getting increasingly recognized. However, it is unclear whether and how non-proliferative diabetic retinopathy (NPDR) is affected by Interleukin-17A (IL-17A) and Interleukin-22 (IL-22), two well-known inflammatory factors, and irisin, a novel potential anti-inflammatory factor. Here we recruited 40 type 2 diabetes mellitus (T2DM) patients with NPDR, 60 T2DM patients without DR (no-DR), and 20 normal glucose tolerance (NGT) controls. Serum levels of IL-17A, IL-22, and irisin were examined. Compared with NGT and no-DR subjects, NPDR group had significantly higher IL-17A levels. Irisin levels were significantly lower in T2DM patients, while IL-22 levels were not significantly different across all three groups. Multiple logistic regression analysis revealed that IL-17A significantly increased the risk of NPDR (OR = 1.22, P < 0.05) before adjusting for irisin. When irisin was included in the model, neither irisin nor IL-17A was associated with NPDR. Further partial correlation analysis showed that irisin was intrinsically correlated with IL-17A even after multiple adjustment (r = -0.252; P = 0.018). These findings suggest that IL-17A is an independent risk factor of NPDR, and irisin could protect against DR through potential anti-IL-17A effects.
Irisin Inhibits Atherosclerosis by Promoting Endothelial Proliferation Through microRNA126-5p.
Zhang Yuzhu,Song Haibo,Zhang Yuan,Wu Fei,Mu Qian,Jiang Miao,Wang Fang,Zhang Wen,Li Liang,Shao Lei,Li Shiwu,Yang Lijun,Zhang Mingxiang,Wu Qi,Tang Dongqi
Journal of the American Heart Association
BACKGROUND:Irisin is a newly discovered myokine that has been considered a promising candidate for the treatment of cardiovascular disease through improving endothelial function. However, little is known about the role of irisin in the progression of atherosclerosis. METHODS AND RESULTS:We used a carotid partial ligation model of apolipoprotein E-deficient mice fed on a high-cholesterol diet to test the anti-atherosclerosis effect of irisin. Irisin treatment significantly suppressed carotid neointima formation. It was associated with increased endothelial cell proliferation. In addition, irisin promoted human umbilical vein endothelial cell survival via upregulating microRNA126-5p expression through the ERK signaling pathway. Inhibition of microRNA126-5p using the microRNA126-5p inhibitor abolished the prosurvival effect. The same results were demonstrated in vivo as the expression of microRNA126-5p noticeably increased in ligated carotid artery after irisin treatment. Furthermore, in vivo blockade of microRNA126-5p expression using the antagomir abolished the inhibitory effects of irisin on neointima formation, lesional lipid deposition, macrophage area, and the pro-proliferation effects on endothelial cells. CONCLUSIONS:Taken together, our study demonstrates that irisin significantly reduces atherosclerosis in apolipoprotein E-deficient mice via promoting endothelial cell proliferation through microRNA126-5p, which may have a direct therapeutic effect on atherosclerotic diseases.
The Myokine Irisin Is Released in Response to Saturated Fatty Acids and Promotes Pancreatic β-Cell Survival and Insulin Secretion.
Natalicchio Annalisa,Marrano Nicola,Biondi Giuseppina,Spagnuolo Rosaria,Labarbuta Rossella,Porreca Immacolata,Cignarelli Angelo,Bugliani Marco,Marchetti Piero,Perrini Sebastio,Laviola Luigi,Giorgino Francesco
This study explored the role of irisin as a new pancreatic β-cell secretagogue and survival factor and its potential role in the communication between skeletal muscle and pancreatic β-cells under lipotoxic conditions. Recombinant irisin stimulated insulin biosynthesis and glucose-stimulated insulin secretion (GSIS) in a PKA-dependent manner and prevented saturated fatty acid-induced apoptosis in human and rat pancreatic β-cells, as well as in human and murine pancreatic islets, via AKT/BCL2 signaling. Treatment of myotubes with 0.5 mmol/L palmitate for 4 h, but not with oleate, promoted an increase in irisin release in the culture medium. Moreover, increased serum levels of irisin were observed in mice fed with a high-fat diet. Mouse serum rich in irisin and the conditioned medium from myotubes exposed to palmitate for 4 h significantly reduced apoptosis of murine pancreatic islets and insulin-secreting INS-1E cells, respectively, and this was abrogated in the presence of an irisin-neutralizing antibody. Finally, in vivo administration of irisin improved GSIS and increased β-cell proliferation. In conclusion, irisin can promote β-cell survival and enhance GSIS and may thus participate in the communication between skeletal muscle and β-cells under conditions of excess saturated fatty acids.
The Effect of n-3 Polyunsaturated Fatty Acids Supplementation on Serum Irisin in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Trial.
Ansari Samaneh,Djalali Mahmoud,Mohammadzadeh Honarvar Niyaz,Mazaherioun Maryam,Zarei Mahnaz,Agh Fahimeh,Gholampour Zahra,Javanbakht Mohammad Hassan
International journal of endocrinology and metabolism
BACKGROUND:Diabetes refers to a group of metabolic diseases with blood glucose of higher than normal ranges. Furthermore, n-3 polyunsaturated fatty acids are necessary for the regulation of the activity of human function. The effect of n-3 PUFA on diabetes has been investigated in animal studies, yet, the exact amount has not been set, to date. Irisin, as a new myokine, is released from skeletal muscle and Irisin levels decrease as a result of physical inactivity, overweightness, and obesity. Also, the reduction of serum irisin level is associated with development of insulin resistance and type 2 diabetes. This study was performed to assess the effects of n-3 PUFA supplementation on serum irisin level in patients with diabetes. METHODS:This randomized clinical trial included 43 patients with type 2 diabetes (21 patients in the placebo group and 22 patients in the n-3 PUFA supplement group). They were randomized to groups, one receiving 10 weeks of either n-3 PUFA supplement and the other the placebo (1250 mg capsule, three times per day). Samples were also matched by age, gender, and body mass index (BMI) in the 2 groups. Anthropometric measurements, demographic information and dietary intakes were obtained both before and after the intervention. Serum irisin levels were measured before and after the intervention using human irisin enzyme linked immunosorbent assay (ELISA) kit. Independent t-test was used to compare the mean outcomes between groups. RESULTS:At baseline, irisin serum levels were not significantly different between the placebo and n-3 PUFA supplementation groups (P > 0.05). However, a significant change was observed between the groups after intervention (P = 0.04). Also there was a significant difference in mean change (after versus before the intervention) (P = 0.05). Compared to the placebo, n-3 PUFA supplementation decreased serum FBS and HbA1C (P = 0.036 and 0.001; respectively). Also, there were significant differences between changes of diastolic blood pressure and HOMA-IR after the intervention between the groups. The duration of illness was not considered as a confounding factor because there was no significant association between irisin level (after versus before the intervention) and the illness duration. CONCLUSIONS:The current study indicated that n-3 PUFA supplementation with a dosage of 1250 mg three times per day, resulted in increased serum irisin level of diabetic patients.
Association of irisin and FNDC5 rs16835198 G>T gene polymorphism with type 2 diabetes mellitus and diabetic nephropathy. An Egyptian pilot study.
Khidr Emad Gamil,Ali Shawkey Saddik,Elshafey Mostafa Mahmoud,Fawzy Olfat Ahmed
Diabetes mellitus is a fast-growing health problem in Egypt affecting morbidity, mortality and health care resources. Irisin, a new exercise-induced myokine inducing browning of white adipose tissues, has gained a great interest as a potential new target for combating type 2 diabetes mellitus (T2DM) and its complications. In this study, we assessed serum irisin levels in T2DM and diabetic nephropathy to elucidate possible relationships between irisin and metabolic parameters and renal functions. We also investigated, for the first time in Egypt, the association of FNDC5 rs16835198 G>T polymorphism with T2DM, diabetic nephropathy and irisin levels. One hundred type 2 diabetic patients (40 normoalbuminuric and 60 with nephropathy) as well as fifty control subjects were enrolled in this study. Serum irisin and insulin were evaluated by ELISA. Genomic DNA was genotyped for FNDC5 rs16835198 polymorphism using TaqMan genotyping assay. Serum irisin levels were lower in diabetic patients compared to controls and this decrease was more pronounced in diabetic nephropathy. Irisin correlates with metabolic parameters and renal functions. Frequencies of T allele and TT genotype were significantly lower among T2DM and diabetic nephropathy patients compared to controls. Moreover, G allele was associated with elevated insulin resistance and dyslipidemia without effect on circulating irisin levels. IN CONCLUSION:T2DM and diabetic nephropathy are associated with decreased levels of irisin. FNDC5 rs16835198 TT genotype associates with decreased risk of T2DM in Egyptians with no effect on renal complications. Also, G allele has insulin desensitizing action with no association with circulating irisin levels.
The role of irisin in the relationship between psoriasis and insulin resistance.
Bulur Isil,Erdogan Hilal K,Kocatürk Evin,Saracoglu Zeynep N,Alataş Özkan,Yildiz Pınar,Bilgin Muzaffer
Giornale italiano di dermatologia e venereologia : organo ufficiale, Societa italiana di dermatologia e sifilografia
BACKGROUND:Irisin, a hormone like myokine, is identified to the relation with insulin resistance and metabolic syndrome recently. In the literature to date, there are no studies evaluating serum irisin levels in psoriasis patients. We aimed to elucidate the pathogenesis of insulin resistance in psoriasis patients by evaluating serum irisin levels and metabolic parameters associated with insulin resistance in patients with plaque-type psoriasis vulgaris. METHODS:The study included 40 patients with moderate-to-severe chronic plaque-type psoriasis vulgaris and 37 healthy subjects. Body Mass Index (BMI) and waist circumference were measured, and serum irisin, fasting blood glucose (FBG), lipid profile, high-sensitivity CRP (hs-CRP) and insulin levels were assessed. To evaluate insulin resistance, the Homeostasis Model Assessment (HOMA-IR) and triglyceride/HDL (TG/HDL) ratio were used. RESULTS:Serum irisin and HDL levels were significantly lower in patients than the control group (P<0.001, P=0.024). Within the patient group, there was a significant negative correlation between serum irisin and serum TG, LDL, and TG/HDL levels (P=0.041, P=0.022, P=0.025), and a positive correlation with HDL levels (P=0.036). The PASI scores and serum irisin levels were significantly positively correlated. CONCLUSIONS:In conclusion, we observed that serum irisin levels were significantly lower in patients with psoriasis, and associated with serum lipid levels and disease activity in our study. These results can be interpreted that irisin is involved in the disease pathogenesis of patients with psoriasis in relation to metabolic dysregulation.
The relationship between circulating irisin levels and tissues AGE accumulation in type 2 diabetes patients.
Li Zhu,Wang Gang,Zhu Yan-Juan,Li Chen-Guang,Tang Yun-Zhao,Jiang Zhen-Huan,Yang Min,Ni Chang-Lin,Chen Li-Ming,Niu Wen-Yan
Advanced glycation end-products (AGEs), measured by skin autofluorescence (AF), are a factor in the development or worsening of many degenerative diseases, such as diabetes and atherosclerosis. Irisin levels have been associated with diabetes, endothelial dysfunction and atherosclerosis. The objective of the present study was to investigate whether circulating irisin levels are correlated with skin AF values in type 2 diabetes patients. A total of 362 Chinese type 2 diabetic patients and 100 age- and sex-matched healthy controls were recruited in the present study. Clinical characteristics, blood biochemistry and circulating irisin levels were measured. Skin AF was measured using an AGE reader. Circulating irisin levels were significantly lower, while skin AF values were increased in type 2 diabetes compared with controls (<0.05 respectively). By dividing the distribution of skin AF values into tertiles, serum irisin levels gradually lowered with increasing skin AF values (<0.05). After adjusting for covariates, multivariate stepwise regression analysis demonstrated that serum lower irisin levels were independently associated with skin AF (=0.009). Circulating irisin levels were lower in type 2 diabetes patients compared with healthy controls. Lower levels of irisin are independently associated with elevated skin AF values, indicating that circulating irisin levels could be associated with AGEs accumulation, which is one of the reasons causing vascular complications in diabetic patients.
β-arrestin-2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling.
Pang Yaling,Zhu Haihui,Xu Jianqin,Yang Lihua,Liu Lingjiao,Li Jing
Experimental cell research
Type 2 diabetes mellitus (T2DM) is a common metabolic disease worldwide. It has been reported that irisin play regulatory role in glucose metabolism in T2DM. However, the underlying mechanism involved in that is not completely known. Herein, we determined the novel role of β-arrestin-2 in irisin-induced glucose utilization in diabetes. Effects of irisin and β-arrestin-2 on glucose utilization were investigated in a rat model of diabetes and in diabetic C2C12 cells in vitro. Results showed that irisin had positive role in glucose metabolism via regulating glucose tolerance as well as uptake in cardiac and skeletal muscle tissues, as evidenced by IPGTT, 2-deoxyglucose uptake and plasma membrane GLUT-4 assay. β-arrestin-2 also improved glucose utilization in diabetes by increasing the glucose uptake and insulin sensitivity, as shown in mice overexpressing β-arrestin-2. In diabetic C2C12 myocytes, irisin-induced GLUT4 and glucose uptake were restrained by β-arrestin-2 inhibition, but was enhanced by β-arrestin-2 overexpression. Additionally, irisin and β-arrestin-2 increased the activation of p38 MAPK in diabetic C2C12 cells, and the repression of p38 MAPK activation decreased the glucose uptake and plasma membrane GLUT-4 was enhanced by irisin and β-arrestin-2 overexpression in diabetic C2C12 cells. In conclusion, we demonstrated that β-arrestin-2 has a crucial role in irisin induced glucose metabolism in T2DM by regulating the p38 MAPK signaling. This might present a novel therapeutic target of treatment for human diabetes.
A Review on the Role of Irisin in Insulin Resistance and Type 2 Diabetes Mellitus.
Gizaw Mamo,Anandakumar Pandi,Debela Tolessa
Journal of pharmacopuncture
Irisin is a novel hormone like polypeptide that is cleaved and secreted by an unknown protease from fibronectin type III domain-containing protein 5 (FNDC5), a membrane- spanning protein and which is highly expressed in skeletal muscle, heart, adipose tissue, and liver. Since its discovery in 2012, it has been the subject of many researches due to its potent physiological role. It is believed that understanding irisin's function may be the key to comprehend many diseases and their development. Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Irisin is a powerful messenger, sending the signal to determine the function of specific cells, like skeletal muscle, liver, pancreas, heart, fat and the brain. The action of irisin on different targeted tissues or organs in human being has revealed its physiological functions for promoting health or executing the regulation of variety of metabolic diseases. Numerous studies focus on the association of irisin with metabolic diseases which has gained great interest as a potential new target to combat type 2 diabetes mellitus and insulin resistance. Irisin is found to improve insulin resistance and type 2 diabetes by increasing sensitization of the insulin receptor in skeletal muscle and heart by improving hepatic glucose and lipid metabolism, promoting pancreatic β cell functions, and transforming white adipose tissue to brown adipose tissue. This review is a thoughtful attempt to summarize the current knowledge of irisin and its effective role in mediating metabolic dysfunctions in insulin resistance and type 2 diabetes mellitus.
Study of Irisin Hormone Level in Type 2 Diabetic Patients and Patients with Diabetic Nephropathy.
Shelbaya Salah,Abu Shady Manal Mohamed,Nasr Merhan Samy,Bekhet Meram Mohamed,Mageed Yasmine Abd-Al,Abbas Magdy
Current diabetes reviews
BACKGROUND:Type 2 diabetic patients with diabetic nephropathy are associated with multifactorial abnormal energy metabolism. Irisin has been recently introduced as a hormone that is exercise-induced and is secreted by skeletal muscles. It is hypothesized that patients with chronic kidney disease usually have abnormal irisin levels. AIM:We aimed to study the level of Irisin hormone in patients with type 2 diabetes and to document that it is related to diabetic nephropathy. METHODS:The current study included 60 subjects with type 2 diabetes and 30 healthy subjects as a control group. Diabetic subjects were divided into 30 without diabetic complications and 30 with diabetic nephropathy (DN). Serum Irisin levels, fasting blood glucose (FBG), 2hours plasma glucose (2hPG), hemoglobin A1c (HbA1c), kidney functions including serum creatinine and albumin/ creatinine ratio were assessed. RESULTS:There was a statistically significant decrease in Irisin levels in diabetic patients compared to controls (34.46 ± 15.28 ng/ml vs. 152.600 ± 39.581 ng/ml, p<0.001). Irisin levels were lower in diabetic patients with DN than in those without complications (20.967 ± 4.476 ng/ml vs. 47.967 ± 8.853 ng/ml, p<0.01). There was a statistically significant negative correlation between irisin and serum creatinine (r=-0.729), systolic blood pressure (r=-0.493), diastolic blood pressure (r=-0.625), duration of diabetes (r=-0.942), BMI(r=-0.396), albumin/creatinine ratio (r=-0.696), and HbA1c (r=-0.305) in all type 2 diabetic patients (p<0.05). On performing multivariate regression analysis, we found that the duration of diabetes was the only independent determinant of irisin level. CONCLUSION:There is a decrease in serum irisin level in type 2 diabetic patients with even more significant reduction in patients with diabetic nephropathy.
Association of Irisin Circulating Level with Diabetic Retinopathy: A Case-Control Study.
Tarboush Nafez Abu,Abu-Yaghi Nakhleh E,Al Ejeilat Laith H,Wahed Rawand K Abdel,Jeris Issa N
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
Obesity and obesity induced type 2 diabetes development and progression have been associated with sedentary lifestyle. Irisin, a newly discovered myokine, has been demonstrated at lower levels in obese and type 2 diabetes patients compared to controls. The main aim of this study is to explore association of Irisin with diabetic retinopathy (DR). A total of 233 healthy and adults participated in this study. Participants were divided into four categories: a healthy control group and an age-match subset of patients with type 2 diabetes; a positive control group of patients with type 2 diabetes not affected by DR (No DR); and patients with type 2 diabetes affected by DR (non-proliferative DR (NPDR) and proliferative DR (PDR)). Plasma samples were quantified for Irisin measurement, lipid profile and HbA1c. Comparison of the age-matched groups of healthy controls and patients with type 2 diabetes revealed lower Irisin plasma level in type 2 diabetes group. Analyses revealed negative correlations of Irisin to HbA1c and LDL levels and positive correlation to HDL level. Comparing Irisin level in No DR and DR groups revealed a higher level in No DR group and analysis per DR classification indicated higher Irisin level in NPDR group. Our results demonstrate not only correlation of plasma Irisin level with DR stages, but also significantly different Irisin level among them. This is promising in terms of researching Irisin as a potential associating marker for type 2 diabetes and DR development and progression.
Irisin inhibits high glucose-induced endothelial-to-mesenchymal transition and exerts a dose-dependent bidirectional effect on diabetic cardiomyopathy.
Liu Xue,Mujahid Haroon,Rong Bing,Lu Qing-Hua,Zhang Wei,Li Peng,Li Na,Liang Er-Shun,Wang Qi,Tang Dong-Qi,Li Nai-Lin,Ji Xiao-Ping,Chen Yu-Guo,Zhao Yu-Xia,Zhang Ming-Xiang
Journal of cellular and molecular medicine
Emerging evidence indicates that irisin provides beneficial effects in diabetes. However, whether irisin influences the development of diabetic cardiomyopathy (DCM) remains unclear. Therefore, we investigated the potential role and mechanism of action of irisin in diabetes-induced myocardial dysfunction in mice. Type 1 diabetes was induced in mice by injecting streptozotocin, and the diabetic mice were administered recombinant r-irisin (low or high dose: 0.5 or 1.5 μg/g body weight/day, I.P.) or PBS for 16 weeks. Irisin treatment did not alter blood glucose levels in the diabetic mice. However, the results of echocardiographical and histopathological assays indicated that low-dose irisin treatment alleviated cardiac fibrosis and left ventricular function in the diabetic mice, whereas high-dose irisin failed to mitigate the ventricular function impairment and increased collagen deposition. The potential mechanism underlying the effect of low-dose irisin involved irisin-mediated inhibition of high glucose-induced endothelial-to-mesenchymal transition (EndMT); conversely, high-dose irisin treatment enhanced high glucose-induced MMP expression by stimulating MAPK (p38 and ERK) signalling and cardiac fibroblast proliferation and migration. Low-dose irisin alleviated DCM development by inhibiting high glucose-induced EndMT. By contrast, high-dose irisin disrupted normal MMP expression and induced cardiac fibroblast proliferation and migration, which results in excess collagen deposition. Thus, irisin can inhibit high glucose-induced EndMT and exert a dose-dependent bidirectional effect on DCM.
The Role of Irisin, Insulin and Leptin in Maternal and Fetal Interaction
Ökdemir Deniz,Hatipoğlu Nihal,Kurtoğlu Selim,Siraz Ülkü Gül,Akar Himmet Haluk,Muhtaroğlu Sabahattin,Kütük Mehmet Serdar
Journal of clinical research in pediatric endocrinology
Objective:Insulin is an important hormone for intrauterine growth. Irisin is an effective myokine in the regulation of physiological insulin resistance in pregnancy. Leptin and insulin are associated with fetal growth and fetal adiposity. In this study, we aimed to investigate the relationships between irisin, insulin and leptin levels and maternal weight gain, as well as anthropometric measurements in the newborn. Methods:Eighty-four mothers and newborns were included in the study. Irisin, leptin and insulin levels were measured in the mothers and in cord blood. Anthropometric measurements in the newborn, maternal weight at the beginning of the pregnancy and at delivery were recorded. Results:Birth weight were classified as small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA). There was no difference in irisin levels among the groups. Leptin and insulin levels were found to change significantly according to birth weight (p=0.013, and p=0.012, respectively). There was a negative correlation between the anthropometric measurements of the AGA newborns and irisin levels. This correlation was not observed in SGA and LGA babies. Leptin levels were associated with fetal adiposity. Conclusion:While irisin levels are not affected by weight gain during pregnancy nor by birth weight, they show a relationship with anthropometric measurements in AGA infants. These results may lead to the understanding of metabolic disorders that will occur in later life.
Lower circulating irisin is associated with nonalcoholic fatty liver disease and type 2 diabetes.
Shanaki Mehrnoosh,Moradi Nariman,Emamgholipour Solaleh,Fadaei Reza,Poustchi Hossein
Diabetes & metabolic syndrome
Irisin, a novel adipokine secreted by adipose tissue, is hypothesized to play a crucial role in metabolism. The objective of this study was to determine the plasma levels of irisin and adiponectin in patients with NAFLD (n=41), T2DM (n=41) and NAFLD with T2DM (NAFLD+T2DM) (n=40) in comparison with healthy subjects (n=40) and also to investigate the possible association of irisin levels with NAFLD and diabetes-related indices. The anthropometric and biochemical parameters were measured in all subjects. Plasma levels of irisin and adiponectin were measured by ELISA. The levels of irisin was significantly lower in NAFLD, T2DM and NAFLD+T2DM patients, compared to the controls (p<0.001). Irisin levels were negatively correlated with BMI, WHR, visceral fat, HOMA-IR, FBG, insulin, liver stiffness and liver enzymes. We also observed a positive correlation between plasma levels of adiponectin and irisin. Based on multiple stepwise linear regression, ALT (β [SE]=0 0.056 [0.012], p<0.001) and irisin concentrations (β [SE]=-1.672 [0.414], p<0.001) were two independent predictors for liver stiffness. Moreover, increased irisin was associated with reduce the risk of T2DM, NAFLD and NAFLD+T2DM. The receiver operating characteristic (ROC) curves analysis for diagnostic value of irisin circulating levels to differentiate between each condition also showed that the area under the curve were 0.78 for NAFLD, 0.8 forT2DM, and 0.86 for T2DM+NAFLD. It seems that the decreased circulating levels of irisin and adiponectin might be associated with T2DM and NAFLD.
Plasma Irisin Levels in Subjects with Type 1 Diabetes: Comparison with Healthy Controls.
Tentolouris Anastasios,Eleftheriadou Ioanna,Tsilingiris Dimitrios,Anastasiou Ioanna A,Kosta Ourania A,Mourouzis Iordanis,Kokkinos Alexandros,Pantos Constantinos,Katsilambros Nikolaos,Tentolouris Nikolaos
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme
Irisin is a myokine that increases energy expenditure. In this cross-sectional study, we examined for differences in plasma irisin concentrations between subjects with type 1 diabetes mellitus and healthy individuals and searched for associations between plasma irisin levels and clinical and biochemical characteristics as well as self-reported physical activity. A total of 79 subjects with type 1 diabetes [age 38.2±12.5 years, men/women (n): 27/52], were consecutively recruited. Moreover, 53 healthy controls, matched for age and body mass index with those with diabetes were recruited. Plasma irisin was measured with ELISA. Participants were asked about their physical activity during the last week. We also measured trunk and visceral fat. Circulating irisin levels were lower in subjects with diabetes than in controls [median value (interquartile range): 53.0 (35.2, 106.3) vs. 178.1 (42.6, 641.6) ng/ml, respectively, p<0.001]. In the group of diabetes, univariate analysis showed that irisin levels were associated with waist circumference (beta=-0.283, p=0.023), serum triglycerides (beta=-0.282, p=0.031), and trunk fat (beta=-0.324, p=0.012). In multivariate analysis after adjustment for potential confounders, irisin levels were associated independently only with waist circumference (beta=-0.403, p=0.005). Among controls, multivariate analysis demonstrated that irisin levels were associated with pack-years of smoking (beta=-0.563, p=0.012) and fasting triglycerides (beta=-0.338, p=0.041). Circulating irisin levels were lower in subjects with diabetes in comparison with healthy-matched controls. In conclusion, plasma irisin concentrations in subjects with diabetes were associated with waist circumference, while in controls with serum triglycerides and pack-years of smoking.
Irisin and leptin concentrations in relation to obesity, and developing type 2 diabetes: A cross sectional and a prospective case-control study nested in the Normative Aging Study.
Sahin-Efe Ayse,Upadhyay Jagriti,Ko Byung-Joon,Dincer Fadime,Park Kyung Hee,Migdal Alexandra,Vokonas Pantel,Mantzoros Christos
Metabolism: clinical and experimental
OBJECTIVE:To investigate the associations between irisin and leptin levels in obesity and insulin resistance in a cross sectional study. To assess the potential role of irisin and leptin as a predictive marker of T2DM using a nested case-control study. METHODS:Both studies were designed within the longitudinal VA NAS cohort. The cross sectional study involved 111 non obese and 105 obese subjects who were subdivided into two groups based on their fasting glucose tolerance. In the nested 1:3 case-control study, 47 subjects with T2DM and 140 non-diabetic controls were selected. Serum samples collected 3-5 years before the diagnosis of T2DM were analyzed. Irisin and leptin concentrations were measured using a validated ELISA and radioimmunoassay respectively. RESULTS:In the cross-sectional study, irisin did not differ between groups based on their fasting glucose tolerance. When subjects were grouped based on obesity status, both irisin and leptin concentrations were significantly higher in obese compared to the non-obese group (p=0.03 and <0.001, respectively). Irisin concentrations positively correlated with leptin concentrations (r= 0.392, P < 0.001). In the nested case control study, leptin concentrations were a significant predictor of developing diabetes (p=0.005) in unadjusted models, but not after correcting for BMI, whereas irisin concentrations did not play a role of comparable significance. CONCLUSIONS:Leptin concentrations are higher in the obese group irrespective of their glucose tolerance. Obese individuals with impaired fasting glucose have higher concentrations of circulating irisin compared to non-obese subjects with normal glucose tolerance. Irisin concentrations do not predict risk of developing diabetes prospectively.
Fibroblast Growth Factor 21, Adiponectin, and Irisin as Markers of Unfavorable Metabolic Features in 12-Year-Old Children.
Seppä Satu,Tenhola Sirpa,Voutilainen Raimo
Journal of the Endocrine Society
Context:Among cytokines, fibroblast growth factor 21 (FGF21), adiponectin (Adn), and irisin have been considered potential biomarkers for insulin sensitivity (IS). Objective:We evaluated whether serum FGF21, Adn, and irisin associate with markers of IS and serum lipids in 12-year-old children. Design Participants and Main Outcome Measures:This cohort study included 192 12-year-old children (109 girls). Seventy-eight of them had been born appropriate for gestational age (AGA), 70 small for gestational age (SGA), and 44 from preeclamptic pregnancies (PREs) as AGA. Fasting serum FGF21, Adn, irisin, lipids, inflammatory markers, and IS markers were measured. Quantitative insulin sensitivity check index (QUICKI) was calculated. Results:The means of serum FGF21, high molecular weight (HMW) Adn, and irisin did not differ between the sexes or between the SGA, AGA, and PRE children. In the whole study population, FGF21 associated positively with irisin and uric acid and negatively with leptin and high-density lipoprotein cholesterol (HDL-C). HMW Adn associated positively with total Adn, HDL-C, leptin, and SHBG. Apart from FGF21, irisin associated positively with insulin, high-sensitivity C-reactive protein, -glutamyltransferase, and triglycerides, and negatively with QUICKI, SHBG, and IGF binding protein-1. In multivariate regression analyses, irisin predicted lower IS and HMW Adn predicted higher HDL-C body mass index-independently, whereas FGF21 had no independent contribution to IS or lipid variables. Conclusion:In 12-year-old children, serum irisin was associated with markers reflecting reduced IS. HMW Adn predicted HDL-C, whereas FGF21 did not contribute to IS or lipid parameters in multivariate regression analyses.
Association between Irisin, hs-CRP, and Metabolic Status in Children and Adolescents with Type 2 Diabetes Mellitus.
Elizondo-Montemayor Leticia,Gonzalez-Gil Adrian M,Tamez-Rivera Oscar,Toledo-Salinas Carla,Peschard-Franco Mariana,Rodríguez-Gutiérrez Nora A,Silva-Platas Christian,Garcia-Rivas Gerardo
Mediators of inflammation
Proinflammatory cytokines and the novel myokine irisin, a cleavage product of FNDC5, have been found to play a role in obesity and type 2 diabetes mellitus (T2DM). Irisin has been shown to increase browning of adipose tissue, thermogenesis, energy expenditure, and insulin sensitivity, yet its association with inflammatory markers is still limited. Circulating irisin has been found to be increased in obesity, while in adult subjects with T2DM decreased levels have been found. However, data establishing the association of circulating irisin in children and adolescents with T2DM has not been described in the literature. The objective of this study was to determine irisin plasma concentration and its association with metabolic and adiposity markers and with hs-CRP, a surrogate marker of inflammation used in clinical practice, in a pediatric population with T2DM. A cross-sample of 40 Mexican children and adolescents aged 7-17 were recruited, 20 diagnosed with T2DM and 20 healthy controls. Plasma irisin levels were found to be lower in the T2DM group compared with controls, which could be attributed to a reduced PGC-1 activity in muscle tissue with a consequent decrease in FNDC5 and irisin expression. Irisin concentration was found to be positively correlated with HDL-c, LDL-c, and total cholesterol, while negatively correlated with BMI, waist circumference, and triglycerides. However, after multiple regression analysis, only HDL-c correlation remained significant. hs-CRP was higher in the T2DM group and positively associated with adiposity markers, unfavorable lipid profile, insulin levels, and HOMA-IR, but no association with irisin was found. Given the favorable metabolic effects attributed to irisin, the low plasma levels found in children and adolescents with T2DM could exacerbate the inflammatory and metabolic imbalances and the intrinsic cardiovascular risk of this disease. We propose an "irisin-proinflammatory/anti-inflammatory axis" to explain the role of irisin as a metabolic regulator in obesity and T2DM.
Colostrum and mature breast milk analysis of serum irisin and sterol regulatory element-binding proteins-1c in gestational diabetes mellitus.
Fatima Syeda Sadia,Khalid Erum,Ladak Asma Akbar,Ali Syed Adnan
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians
We aimed to evaluate irisin and SREBP-1c levels in serum, colostrum and mature breast milk in women with and without gestational diabetes (GDM); and to relate them with maternal glucose, lipid profile and weight status of babies. GDM positive women ( = 33) and normal glucose tolerant women (NGT) ( = 33) were recruited. Maternal blood samples were collected at 28th week of gestation and later at 6-week post-partum while breast milk samples of the lactating mothers were collected within 72 hours of birth (colostrum) and at 6 weeks post-partum (mature milk). Irisin and SREBP-1c levels were analyzed by commercially available ELISA kits for all maternal samples. Lower levels of irisin were seen in serum, colostrum and mature breast milk of GDM females ( < .01). SREBP-1c profile showed a similar trend of low serum levels in GDM, however, they were undetectable in colostrum and mature breast milk. Weak to moderate correlations of serum irisin with BMI ( = 0.439; < .001), GTT 0 hours ( = 0.403; = .01), HbA1c ( = -0.312; = .011), Fasting blood glucose ( = 0.992; = .008), and baby weight at birth ( = 0.486; < .001). Colostrum and mature breast milk irisin showed positive associations with baby weight at 6 weeks ( = 0.325; = .017; = 0.296; = .022, respectively). Serum SREBP-1c at 6 weeks correlated with random blood glucose ( = 0.318; = .009), and HbA1c (= -0.292; = .011). All correlations were lost once we adjusted for maternal BMI. Low irisin and SREBP1-c levels may favor development of GDM in pregnant subjects. Further, low mature breast milk levels may act as a continued stressor from fetal to infant life as long as breast-feeding is continued. Further studies are required to identify the mechanistic relationship between these biomarkers and GDM.
Irisin reverses insulin resistance in C2C12 cells via the p38-MAPK-PGC-1α pathway.
Ye Xiao,Shen YiMin,Ni Chao,Ye Jun,Xin Yubo,Zhang Wei,Ren YueZhong
Insulin resistance (IR) is a fundamental pathogenic factor shared by a myriad of metabolic disorders, including obesity and type 2 diabetes. The mechanism of IR is usually accompanied by mitochondrial dysfunction. Irisin has been proposed to act as a hormone in the regulation of energy homeostasis and metabolism. However, the effects of irisin on IR and mitochondrial function have not yet been fully investigated. Here, our research shows that irisin increases glucose uptake in C2C12 myoblast cells via the p38-mitogen-activated protein kinase (MAPK)-PGC-1α pathway. Irisin can also enhance mitochondrial function and mitochondrial respiration. Moreover, irisin stimulates autophagy via PGC-1α. Collectively, these data provide basic evidence to support the therapeutic potential of irisin for IR, which may rely on p38-MAPK-PGC-1α pathway activation and enhance mitochondrial function.
Irisin and Visfatin Predicts Severity of Diabetic Nephropathy.
Mageswari Ramalingam,Sridhar M G,Nandeesha H,Parameshwaran Sreejith,Vinod K V
Indian journal of clinical biochemistry : IJCB
Although the roles of irisin and visfatin have been well established in diabetes mellitus, there are limited studies about their association in diabetic nephropathy. The present study was designed to assess the levels of irisin and visfatin and their association with the severity of diabetic nephropathy. 43 diabetic nephropathy cases and 43 diabetic subjects without nephropathy were enrolled in the study. Serum levels of irisin and visfatin were compared in both the groups. Irisin and visfatin were significantly increased in diabetic nephropathy cases when compared with diabetes subjects without nephropathy. eGFR was negatively correlated with visfatin (r = -0.323, = 0.034), irisin (r = -0.324, = 0.034), urine albumin (r = -0.443, = 0.003) and albumin creatinine ratio (r = -0.419, = 0.005) in patients with diabetic nephropathy. Visfatin was significantly elevated in stage IV nephropathy compared with stage III nephropathy. We conclude that irisin and visfatin are elevated in diabetic nephropathy and can be an index of its severity.
High irisin levels are associated with better glycemic control and bone health in children with Type 1 diabetes.
Faienza Maria Felicia,Brunetti Giacomina,Sanesi Lorenzo,Colaianni Graziana,Celi Monica,Piacente Laura,D'Amato Gabriele,Schipani Ernestina,Colucci Silvia,Grano Maria
Diabetes research and clinical practice
AIM:Irisin is a new peptide produced mainly by the skeletal muscle playing an important role both in glucose/energy homeostasis and bone metabolism. Childhood type 1 diabetes mellitus (T1DM) is associated with decreased bone mass. We aimed to evaluate irisin levels in TD1M children and their correlation with bone metabolism and glycaemic control. METHODS:Ninety-six T1DM subjects (12.2 ± 4 years), 56 on multiple daily injections (MDI), 40 on continuous subcutaneous insulin infusion (CSII), and 34 controls were included in the study. Irisin and bone remodeling markers were quantified in sera from patients and controls. Bone mineral density (BMD) was evaluated by QUS. RESULTS:Increased irisin levels were found in T1DM patients respect to controls (p < 0.001). With adjustment for age, irisin levels significantly correlated negatively with HbA1c% (r = -0.105, p < 0.001), years of diabetes (r = -0.07, p < 0.04), 25(OH)-Vitamin D (r = -0.175, p < 0.0001), and positively with BTT-Z-score (r = 0.088, p = 0.016), and osteocalcin (r = 0.059, p < 0.04). We detected the highest levels of irisin in CSII patients compared to MDI and controls (p < 0.001 and p < 0.007 respectively). CONCLUSIONS:We demonstrated high irisin levels in T1DM children and the association of highest irisin amounts to a better glycaemic control and bone health in TDM1 subjects on CSII.
High irisin levels in overweight/obese children and its positive correlation with metabolic profile, blood pressure, and endothelial progenitor cells.
De Meneck F,Victorino de Souza L,Oliveira V,do Franco M C
Nutrition, metabolism, and cardiovascular diseases : NMCD
BACKGROUND AND AIMS:Irisin is involved in the compensatory mechanisms for metabolic regulation and appears to be associated with glucose homeostasis and lipid profile. However, it's possible implications on obesity-associated cardiometabolic complications have not been completely elucidated. This study aimed to investigate the association between irisin level and anthropometric data, metabolic parameters, blood pressure, and endothelial progenitor cells (EPCs) level among children with overweight/obesity. METHODS AND RESULTS:This study included 24 children with overweight/obesity (9 girls and 15 boys) and 63 children with normal weight (25 girls and 38 boys). The anthropometric data, blood pressure, blood biochemistry, EPCs and irisin levels were evaluated. Children with overweight/obesity had significantly higher circulating irisin and EPCs levels than those with normal weight (P < 0.001). Additionally, we found that irisin level was positively correlated with BMI (rho = 0.407), waist circumference (rho = 0.449), triglycerides (rho = .334), glucose (rho = 0.226), insulin (rho = 0.533), HOMA (rho = 0.545), and negatively correlated with HDL cholesterol level (rho = -0.218). Importantly, we also found that irisin levels were significantly correlated with systolic (rho = 0.420), diastolic (rho = 0.331) blood pressure and circulating EPCs level (rho = 0.391). CONCLUSION:Our study provides evidence that overweight/obese children had elevated circulating levels of both irisin and EPCs and address the gap in the literature with regard to the understanding of the implications of irisin on obesity-related cardiometabolic complications among these children and also highlight the possible involvement of irisin regulation on insulin resistance and endothelial function in childhood overweight and obesity.
Reduced plasma level of irisin in first trimester as a risk factor for the development of gestational diabetes mellitus.
Wang Pei,Ma He-Hong,Hou Xiu-Zhen,Song Li-Li,Song Xiao-Long,Zhang Jun-Feng
Diabetes research and clinical practice
BACKGROUND:The aim of this prospective cohort study was to investigate the association of first trimester irisin concentrations and the subsequent development of gestational diabetes mellitus (GDM). METHODS:This cohort study was conducted at three maternity centers in China from July 2015 to June 2016. Data for fasting plasma glucose (FPG) and irisin concentrations in the first trimester and one-step GDM screening with 75-g oral glucose tolerance test (OGTT) performed between 24 and 28 weeks of gestation were collected and analyzed. RESULTS:Plasma from women was available for 1150 women, of whom 135 (11.7%) developed GDM. The median value of irisin in those included women was 141.2 (IQR, 99.4-192.9) ng/ml. In multivariate models comparing the first (Q1), second (Q2) and third (Q3) quartiles against the fourth (Q4) quartile of irisin, levels of irisin in Q1 and Q2 were associated with GDM, and increased risk of GDM by 440% (odds ratios [OR] = 5.40; 95% confidence intervals [CI]: 2.35-11.40) and 283% (OR: 3.83; 95%CI: 1.63-8.01). A model containing known risk factors plus irisin compared with a model containing known risk factors without irisin showed a greater discriminatory ability to predict GDM, the area under the curve (AUC) increased from 0.776 to 0.809. A significant difference in the AUC between the clinical variables alone and the addition of irisin level was observed (difference, 0.034; P = 0.03). CONCLUSIONS:Reduced plasma levels of irisin in first trimester was associated with the increased risk of GDM and might be useful in identifying women at risk for GDM for early prevention strategies.
The association between serum irisin levels and cardiovascular disease in diabetic patients.
Khorasani Zahra Mazloum,Bagheri Ramin Khameneh,Yaghoubi Mohammad Ali,Chobkar Saeed,Aghaee Monavvar Afzal,Abbaszadegan Mohammad Reza,Sahebkar Amirhossein
Diabetes & metabolic syndrome
BACKGROUND:Cardiovascular disease is the most common cause of mortality and morbidity in diabetic patients. Insulin resistance has been shown to be reduced by the secretion of irisin from muscle and adipose tissues. This study was aimed at determining the relationship between serum irisin levels and angiographically defined coronary artery disease (CAD) in type II diabetic patients. METHODS:In this case-control study, 30 diabetic subjects with angiographically defined CAD were compared with 30 age- and sex-matched diabetic subjects without CAD in terms of clinical and laboratory parameters including serum irisin levels. RESULTS:Serum levels of Irisin were significantly higher in the diabetic group without CAD compared with the group with CAD (P = 0.048). Serum irisin levels showed a significant positive correlation with BMI (r = 0.374, P = 0.004) and fasting insulin (r = 0.303, P = 0.021), and a significant negative correlation with diabetes duration (r = -0.384, P = 0.002). Based on the results of the binary logistic regression model, circulating levels of irisin were associated with the presence of CAD in diabetes (p = 0.038) after adjusting for potential confounders. CONCLUSION:Serum irisin levels were lower in the diabetic patients with cardiovascular complication compared with the uncomplicated diabetic patients. Therefore, additional larger scale studies are needed to determine the role of irisin in monitoring CAD in diabetic patients.
Novel adipokines vaspin and irisin as risk biomarkers for cardiovascular diseases in type 2 diabetes mellitus.
El-Lebedy Dalia H,Ibrahim Alshaymaa A,Ashmawy Ingy O
Diabetes & metabolic syndrome
AIMS:Vaspin and irisin are novel cytokines proposed as potential new biomarkers of insulin resistance and endothelial dysfunction. This work is to investigate circulating levels of vaspin and irisin in patients with type 2 diabetes mellitus (T2DM) with and without cardiovascular disease (CVD) to study potential association with disease risk. MATERIALS AND METHODS:Circulating levels of vaspin and irisin were assayed in serum from 135 T2DM patients (with and without CVD) and 70 control subjects by ELISA. RESULTS:Vaspin levels were significantly higher in T2DM patients than in control subjects (6798 ± 3540 pg/ml vs. 3215 ± 3209 pg/ml, p = 0.001) and in CVD patients than in non-CVD patients (7417.3 ± 3507.6 pg/ml vs. 6017.3 ± 3606.4 pg/ml, p = 0.001), with significant positive correlations with BMI, FPG, serum insulin and HOMA-IR. Irisin levels were significantly lower in T2DM patients than in controls (71.15 ± 67.57 ng/ml vs.127 ± 71.57 ng/ml, p = 0.004), and in CVD patients than in non-CVD patients (55.77 ± 54.82 ng/ml vs. 115.5 ± 67 ng/ml, p = 0.003), with significant correlations with HbA1c, HOMA-IR and BMI in diabetic patients, and with HbA1c and TG in CVD patients. Elevated levels of vaspin was associated with 1.7 times increased CVD risk (p = 0.001, OR = 1.7, 95%CI = 1.21-2.39), while lower levels of irisin associated with 1.6 times increased CVD risk (p = 0.007, OR = 1.6, 95%CI = 1.45-2.28). ROC analysis indicated serum vaspin and irisin as independent CVD risk biomarkers with sensitivity, 94% and 73.7%, and specificity, 74% and 74.1%; respectively. CONCLUSION:Our results indicate that circulating vaspin and irisin are potential new independent CVD risk biomarkers in T2DM.
The effects of resistance exercise training followed by de-training on irisin and some metabolic parameters in type 2 diabetic rat model.
Tavassoli Hassan,Heidarianpour Ali,Hedayati Mehdi
Archives of physiology and biochemistry
We investigated the effects of high-fat diet (HFD) consumption combined with diabetes induction, resistance exercise training (RET) and a de-training period on circulating irisin levels and selective metabolic parameters. Rats were assigned to four groups ( 8): healthy non-diabetic rats (NDC), non-diabetic rats that performed RET (NDR), sedentary HFD-fed/STZ-treated rats (HFD/STZ) and HFD-fed/STZ-treated rats that performed RET (HFD/STZ + RE). HFD consumption reduced irisin level and Quicki ( < .01). After the 12-week period, levels of TC, TG, HOMA1-IR, HOMA2-IR and irisin were also lower in the HFD/STZ + RE group compared to the HFD/STZ group. Body weight and HOMA1-IR showed a positive ( 0.558 and 0.538) whereas TC and LDL-C had a negative correlation ( = -0.461 and = -0.630) with irisin level ( < .05). Irisin level increased along with the progress of obesity and T2DM. It seems that RET can attenuate the increase of irisin in those conditions by improvement of glucose/lipid metabolic disorders.
Higher Baseline Serum Irisin Decreases Risk for Body Mass Index Increment in Chinese Populations: A 3.2-Year Cohort Study.
Liu Ruoyi,Shi Lixin,Peng Nianchun,Zhang Qiao,Li Hong
Diabetes therapy : research, treatment and education of diabetes and related disorders
INTRODUCTION:Irisin, a newly discovered myokine, exerts beneficial effects on energy metabolism. However, published results from studies examining the relationship between irisin concentration and obesity have been conflicting. The aim of our study was to investigate the association between serum irisin level and obese individuals with different body mass index (BMI) values and to explore the question of whether serum irisin can predict the risk of increases in the BMI. METHODS:This study based on the data collected in the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION). The cross-sectional cohort study was carried out from May 2011 to August 2011, and a longitudinal cohort study was conducted from July 2014 to October 2014 to complete the first 3.2-year follow-up. We enrolled 93 low-weight subjects (BMI < 18.5 kg/m), 94 normal-weight subjects (BMI 18.5-23.9 kg/m), 98 overweight subjects (BMI 24.0-27.9 kg/m) and 93 obese subjects (BMI ≥ 28 kg/m). Subjects in the normal-weight, overweight and obese groups were selected to match low-weight subjects by age and sex. Serum samples were obtained from all subjects to determine the irisin level. RESULTS:Subjects with a higher serum irisin level tended to have significantly lower changes in BMI and body fat percentage and higher baseline high-density lipoprotein cholesterol level (p < 0.05). No significant correlation was observed between serum irisin level and the baseline obesity index. Serum irisin level was positively correlated to an active lifestyle (i.e. physical activity; β = 1.138, p = 0.032) and negatively correlated to fasting plasma glucose level (β = - 0.996, p = 0.023), changes in BMI (β = - 0.533, p = 0.002), waist circumference (β = - 0.102, p = 0.018), body fat percentage (β = - 0.457, p = 0.001) and Chinese visceral adiposity index (β = - 0.280, p = 0.028). After adjustment for cofactors, higher baseline serum irisin was an independent factor for a decreased BMI increment (baseline serum irisin: odds ratio 0.747, 95% confidence interval 0.652-0.949, p = 0.002). CONCLUSIONS:Higher serum irisin at baseline independently predicted a lower BMI increment in Chinese populations.
Could serum levels of irisin be used in gestational diabetes predicting?
Kulhan Nur Gozde,Kulhan Mehmet,Turkler Can,Ata Nahit,Kiremitli Tunay,Kiremitli Sevil
Taiwanese journal of obstetrics & gynecology
OBJECTIVE:Gestational diabetes mellitus (GDM) is a metabolic disorder during pregnancy leading to acute and chronic complications in both mother and newborn. The pathogenesis of GDM has not been fully understood, However, since the disease shares risk factors with type 2 diabetes mellitus (T2DM), a relationship between these two disease states is plausible. The recently discovered peptide irisin has been hypothesized to be a regulator of body metabolism. However, studies ended up with controversial results. In the present study, we aimed to investigate the relationship between irisin levels and gestational diabetes mellitus and the possible benefits of the metabolic profile. MATERIALS AND METHODS:We performed a cross-sectional analysis of circulating levels of irisin in 100 pregnant women similar for age and body mass index and the groups included 50 gestational diabetic patients and 50 healthy pregnant volunteers. Serum irisin levels were measured by ELISA kit. RESULTS:Mean age and body mass index levels were similar in both groups. Median HbA1c, fasting blood glucose, Glucose 1 h, Glucose 2 h and fasting insülin levels were higher in with gestational diabetic patients compared to the control group. In gestational diabetic group, the median irisin level was lower than in the control group. CONCLUSION:Serum irisin levels were lower in gestational diabetic patients. Further investigations are needed to explore the underlying biological effects of irisin on pregnant women.
FASTING INSULIN AND ALANINE AMINO TRANSFERASE, BUT NOT FGF21, WERE INDEPENDENT PARAMETERS RELATED WITH IRISIN INCREMENT AFTER INTENSIVE AEROBIC EXERCISING.
Torre-Saldaña Viridiana A de la,Gómez-Sámano Miguel Ángel,Gómez-Pérez Francisco Javier,Rosas-Saucedo Juan,León-Suárez Andrés,Grajales-Gómez Mariana,Oseguera-Moguel Jorge,Vega-Beyhart Arturo,Cuevas-Ramos Daniel
Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion
Background:Irisin is a protein cleaved from fibronectin type III domain-containing protein 5 and has been implicated in the beneficial effects of exercise. However, it is unknown which factors contribute to irisin increment after intensive exercising in humans. This study aimed to assess independent factors related with serum irisin after 2 weeks of supervised physical activity in young sedentary healthy women. Design and Methods:We developed a comparative, interventional, longitudinal, and prospective study at a third-level specialty health center. Between March 2010 and August 2011, 82 sedentary young adult women, without chronic diseases or regular medical treatments, were recruited. A total of 38 women fulfilled selection criteria, and irisin concentrations were quantified before and after the intervention. Independent factors related with irisin increment were evaluated according to mild to moderate and vigorous intensity of physical activity. A supervised treadmill exercise test following the Bruce's protocol was conducted from Monday to Friday during 2 weeks. In addition, anthropometric measurements were taken, and fibroblast growth factor 21 (FGF21), glucose, insulin, and liver transaminases were measured. Results:Intensity of exercising was directly related to irisin (p = 0.02) and FGF21 (p = 0.01) serum levels. However, an independent and significant relationship between FGF21 and irisin was not confirmed. A novel association was found between alanine aminotransferase (ALT) and irisin, showing a positive and significant correlation (r = 0.37, p = 0.02). The association was particularly strong with higher intensity of aerobic exercising (r = 0.64, p = 0.01). Linear regression model adjusted for glucose and body mass index confirmed an independent association between ALT and irisin and also between insulin and irisin (adjusted R² = 0.12, p = 0.04). Such association increased after grouping in moderate to vigorous physical activity intensity (adjusted R² = 0.46, F = 4.7, p = 0.03). Conclusions:Serum irisin and FGF21 levels significantly increased after 2 weeks of supervised physical activity. However, only fasting insulin and ALT, but not FGF21, were independent parameters explaining irisin increment, mainly after moderate to vigorous exercising.
Relationship between circulating irisin levels and overweight/obesity: A meta-analysis.
Jia Jue,Yu Fan,Wei Wei-Ping,Yang Ping,Zhang Ren,Sheng Yue,Shi Yong-Qin
World journal of clinical cases
BACKGROUND:Currently, the findings about irisin as a novel myokine related to obesity are inconsistent in overweight/obese people. To our knowledge, no systematic analysis has been conducted to evaluate the relationship between irisin levels and overweight/obesity. AIM:To evaluate the association between circulating irisin levels and overweight/obesity. METHODS:The Cochrane Library, MEDLINE, SCOPUS, and the ISI Web of Science were searched to retrieve all of the studies associated with circulating irisin levels and overweight/obesity. Standard mean difference values and 95% confidence intervals (CI) were estimated and pooled using meta-analysis methodology. RESULTS:A total of 18 studies were included in our meta-analysis containing 1005 cases and 1242 controls. Our analysis showed that the circulating irisin level in overweight/obese people was higher than that in overall healthy controls (random effects MD = 0.63; 95%CI: 0.22-1.05; = 0.003). In the subgroup analysis by ethnicity, the irisin level was higher in overweight/obesity people than that in controls in Africa (random effects MD = 3.41; 95%CI: 1.23-5.59; < 0.05) but not in European, Asian, or American populations. In addition, in a subgroup analysis by age, the results showed that obese children exhibited a higher irisin level than controls (random effects MD = 0.86; 95%CI: 0.28-1.43; < 0.05). CONCLUSION:This meta-analysis provides evidence that circulating irisin is higher in obese individuals compared to healthy controls and it is important to identify the relationship between circulating irisin levels and overweight/obesity in predicting overweight/obesity.
[Correlation among serum levels of Irisin, insulin resistance and abdominal obesityin patients with first-episode schizophrenia].
Zhang P F,Wang Y P,Yuan X X,Tao Q,Liu Y F,Pang L J,Li X,Li H H,Song X Q
Zhonghua yi xue za zhi
To explore the possible role of Irisin in antipsychotic drug-induced insulin resistance and abdominal obesity in patients with schizophrenia and to provide a theoretical basis for the prevention of antipsychotic drug-induced obesity. Fifty-five patients with first-episode schizophrenia, from the First Affiliated Hospital of Zhengzhou University, between January 2016 and December 2017, were admitted as well as fifty healthy controls during the same period. Serum Irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose (FBG), fasting insulin (INS), homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride (TG), total cholesterol (TCHO), highdensity lipoprotein (HDL), low density lipoprotein (LDL) were detected. The average Irisin level ((233±228) mmol/L) was higher than that in the normal control group ((124±89) mmol/L) (<0.05).Repeated measurement analysis of variance showed that the average levels of the height, waist, FBG, INS, TCHO, TG, HDL, LDL, BMI, HOMA-IR and Irisin at the end of the 12(th) and 24(th) week's treatment were higher than baseline (<0.05). After correlation analysis, the level of Irisinat baseline was positively correlated with HOMA-IR (=0.383, <0.05). At the 12(th) week, the level of Irisin was positively correlated with waist circumference, and HOMA-IR (=0.360, =0.475, all <0.05). Multiple linear regression analysis showed that at the 12(th) week's treatment, compared with the baseline period, changes of Irisin was positively correlated with waist circumference and HOMA-IR, respectively (=0.453, =0.420, both <0.05). Irisin may be involved in the process of metabolic regulation and bean early predictor of antipsychotic drug-induced insulin resistance and abdominal obesity.
Construction of a Pichia pastoris strain efficiently secreting irisin and assessment of its bioactivity in HepG2 cells.
Li Xiaodan,Duan Huikun,Liu Qiqi,Umar Muhammad,Luo Wenya,Yang Xingkai,Zhu Jianhong,Li Minggang
International journal of biological macromolecules
Irisin, a circulating myokine, has been shown to effectively ameliorate insulin resistance and type 2 diabetes mellitus by administration of the recombinant protein. Therefore, it is important to efficiently produce active irisin protein and further characterize its potential mechanism against hepatic insulin resistance. In this study, we obtained a multi-copy irisin-expressing P. pastoris strain through an optimized method, which is pH 5.5, 1.8% methanol for 96 h, for producing a high amount of recombinant irisin protein following a series of screening and optimization procedures. The higher-glycosylated irisin, which is supposed to be the active form was obtained by dialysis and ion-exchange chromatography purification method. Both of the laser scanning confocal microscope and the atomic force microscope not only detected the high-effectiveness entering cells of FITC-irisin but also localized it on the membrane of HepG2 cells. Immunofluorescence staining further suggested that irisin could localize in the cytoplasm but not in the nucleus. We further showed that glycosylated irisin rescued palmitate-induced reduction in Glut2 expression and cell viability, inhibited the apoptosis, potentially by activating PI3K/AKT pathway. In summary, we developed an efficient irisin-expressing P. pastoris strain and optimal expression condition, visualized its distribution, demonstrated biological activity and potential mechanisms in hepatic cells.
Increased Expression of Meteorin-Like Hormone in Type 2 Diabetes and Obesity and Its Association with Irisin.
AlKhairi Irina,Cherian Preethi,Abu-Farha Mohamed,Madhoun Ashraf Al,Nizam Rasheeba,Melhem Motasem,Jamal Mohamed,Al-Sabah Suleiman,Ali Hamad,Tuomilehto Jaakko,Al-Mulla Fahd,Abubaker Jehad
Type 2 diabetes (T2D) is a growing pandemic associated with metabolic dysregulation and chronic inflammation. Meteorin-like hormone (METRNL) is an adipomyokine that is linked to T2D. Our objective was to evaluate the changes in METRNL levels in T2D and obesity and assess the association of METRNL levels with irisin. Overall, 228 Arab individuals were enrolled. Plasma levels of METRNL and irisin were assessed using immunoassay. Plasma levels of METRNL and irisin were significantly higher in T2D patients than in non-diabetic patients ( < 0.05). When the population was stratified based on obesity, METRNL and irisin levels were significantly higher in obese than in non-obese individuals ( < 0.05). We found a significant positive correlation between METRNL and irisin (r = 0.233 and = 0.001). Additionally, METRNL and irisin showed significant correlation with various metabolic biomarkers associated with T2D and Obesity. Our data shows elevated METRNL plasma levels in individuals with T2D, further exacerbated with obesity. Additionally, a strong positive association was observed between METRNL and irisin. Further studies are necessary to examine the role of these proteins in T2D and obesity, against their ethnic background and to understand the mechanistic significance of their possible interplay.
In Addition to Poor Glycemic Control, a High Level of Irisin in the Plasma Portends Early Cognitive Deficits Clinically in Chinese Patients With Type 2 Diabetes Mellitus.
Lin Hongyan,Yuan Yang,Tian Sai,Han Jing,Huang Rong,Guo Dan,Wang Jiaqi,An Ke,Wang Shaohua
Frontiers in endocrinology
Irisin plays an important role in the metabolism and homeostasis of energy balance, which is involved in cognitive impairment. This study aimed to investigate the role of irisin in mild cognitive impairment (MCI) among Chinese patients with type 2 diabetes mellitus (T2DM). We recruited 133 Chinese patients with T2DM, and divided them according to the Montreal Cognitive Assessment score. Demographic data were collected and the level of irisin in the plasma was determined. In addition, the results of neuropsychological testing were examined. The concentration of irisin in the plasma was measured using an enzyme immunoassay. A total of 59 patients were diagnosed with MCI and 74 patients were included as healthy-cognition controls. The level of irisin in the plasma ( = 0.043) and homeostasis model of assessment for insulin resistance ( = 0.032) in diabetic patients with MCI were higher than those observed in the healthy controls. A higher level of irisin in the plasma was associated with impaired overall cognition, specifically executive function. Linear regression analysis suggested that irisin ( = 0.017) and glycosylated hemoglobin ( = 0.036) were independent factors of diabetic MCI. The level of irisin in the plasma correlated with cognitive impairment in T2DM patients, particularly with executive function. These results further suggest that, in addition to poor glycemic control, a high level of irisin in the plasma portends early cognitive deficits clinically in Chinese patients with T2DM.