logo logo
Metabolic Abnormalities in Diabetes and Kidney Disease: Role of Uremic Toxins. Koppe Laetitia,Fouque Denis,Soulage Christophe O Current diabetes reports PURPOSE OF REVIEW:Chronic kidney disease (CKD) is characterized by the accumulation of uremic retention solutes (URS) and is associated with perturbations of glucose homeostasis even in absence of diabetes. The underlying mechanisms of insulin resistance, β cell failure, and increase risk of diabetes in CKD, however, remain unclear. Metabolomic studies reported that some metabolites are similar in CKD and diabetic kidney disease (DKD) and contribute to the progression to end-stage renal disease. We attempted to discuss the mechanisms involved in the disruption of carbohydrate metabolism in CKD by focusing on the specific role of URS. RECENT FINDINGS:Recent clinical data have demonstrated a defect of insulin secretion in CKD. Several studies highlighted the direct role of some URS (urea, trimethylamine N-oxide (TMAO), p-cresyl sulfate, 3-carboxylic acid 4-methyl-5-propyl-2-furan propionic (CMPF)) in glucose homeostasis abnormalities and diabetes incidence. Gut dysbiosis has been identified as a potential contributor to diabetes and to the production of URS. The complex interplay between the gut microbiota, kidney, pancreas β cell, and peripheral insulin target tissues has brought out new hypotheses for the pathogenesis of CKD and DKD. The characterization of intestinal microbiota and its associated metabolites are likely to fill fundamental knowledge gaps leading to innovative research, clinical trials, and new treatments for CKD and DKD. 10.1007/s11892-018-1064-7
Management of diabetes mellitus in chronic kidney disease. Garla Vishnu,Kanduri Swetha,Yanes-Cardozo Licy,Lién Lillian F Minerva endocrinologica Diabetes mellitus (DM) and chronic kidney disease (CKD) are two chronic diseases whose prevalence and coprevalence are on the rise. CKD is also the most debilitating and expensive complication of DM while management of DM in CKD is most challenging. CKD is developing in much younger patients with DM, and its presentation is also changing. Various methods of glycemic assessment are affected by CKD and dosage of DM medications needs to be adjusted according to the kidney function. One of the significant barriers to glycemic control in DM patients with CKD is hypoglycemia; close monitoring of glucose levels is essential. Dialysis affects the glucose homeostasis and insulin pharmacokinetics; therefore diabetic medication regimen needs to be adjusted accordingly. Kidney transplants are being increasingly performed as an alternative to dialysis. With the increased survival of transplants secondary to improved immunosuppressive regimen, the prevalence of post-transplant diabetes mellitus is on the increase. Good glycemic control is necessary for the survival of the transplant. 10.23736/S0391-1977.19.03015-3
Kidney: its impact on glucose homeostasis and hormonal regulation. Mitrakou Asimina Diabetes research and clinical practice According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although animal and in vitro studies have documented that the kidney is capable of gluconeogenesis, glucose production by the human kidney has been regarded as negligible. This knowledge is based on net balance measurements across the kidney. Recent studies combining isotopic and balance techniques have demonstrated that the human kidney is involved in the regulation of glucose homeostasis by making glucose via gluconeogenesis, taking up glucose from the circulation, and by reabsorbing glucose from the glomerular filtrate. The human liver and kidneys release approximately equal amounts of glucose via gluconeogenesis in the postabsorptive state. In the postprandial state, although overall endogenous glucose release decreases substantially, renal gluconeogenesis actually increases by approximately 2-fold. Following meal ingestion, glucose utilization by the kidney increases. Increased glucose uptake into the kidney may be implicated in diabetic nephropathy. Normally each day, ∼ 180 g of glucose is filtered by the kidneys; almost all of this is reabsorbed by means of sodium glucose cotransporter 2 (SGLT2), expressed in the proximal tubules. However, the capacity of SGLT2 to reabsorb glucose from the renal tubules is finite and when plasma glucose concentrations exceed a threshold, glucose begins to appear in the urine. Renal glucose release is stimulated by epinephrine and is inhibited by insulin. Handling of glucose by the kidney is altered in type 2 diabetes mellitus (T2DM): renal gluconeogenesis and renal glucose uptake are increased in both the postabsorptive and postprandial states, and renal glucose reabsorption is also increased Since renal glucose release is almost exclusively due to gluconeogenesis, it seems that the kidney is as important gluconeogenic organ as the liver. The most important renal gluconeogenic precursors appear to be lactae glutamine and glycerol. 10.1016/S0168-8227(11)70016-X
Adenosine signaling in diabetes mellitus and associated cardiovascular and renal complications. Peleli Maria,Carlstrom Mattias Molecular aspects of medicine Diabetes mellitus is characterized by abnormal glucose and lipid metabolism, and subsequent hyperglycemia and dyslipidemia, which results from defects in pancreatic islet beta-cells insulin secretion and/or decreased insulin sensitivity in metabolically active organs (i.e. liver, skeletal muscle and adipose tissue). Accumulating evidence highlights a critical role for the adenosine system in the regulation of insulin and glucose homeostasis and the pathophysiology of type 2 diabetes (T2D). Adenosine is a key diverse extracellular signaling molecule that regulates several aspects of tissue function by activating four G-protein-coupled receptors (i.e. A, A, A and A receptors). Moreover, adenosine receptor signaling plays a critical role in inflammation, immune system, and oxidative stress, factors that are also important in metabolic disorders. This review discusses the role of the adenosine receptor system in the development or progression of diabetes mellitus, with specific focus on T2D, and associated complications linked to the cardiovascular and renal systems. 10.1016/j.mam.2016.12.001
Role of Acid-Base Homeostasis in Diabetic Kidney Disease. Khairallah Pascale,Scialla Julia J Current diabetes reports PURPOSE OF REVIEW:Acid-base homeostasis is impaired in chronic kidney disease (CKD) and may contribute to disease progression. Diabetes, a major cause of CKD worldwide, may exacerbate acidosis further due to differences in acid production and excretion. Here, we review the role of abnormal acid-base homeostasis in the pathogenesis and progression of diabetes and diabetic kidney disease. RECENT FINDINGS:Acidosis and dietary acid loading may contribute to the development and worsening of insulin resistance and hypertension, thereby promoting diabetes and diabetic CKD. However, although metabolic acidosis associates with progression of CKD generally, the results in diabetic CKD are mixed. Data suggests that metabolic acid production in diabetes may be higher than would be predicted based on dietary intake alone, and new observational data suggests that this higher diet-independent acid production could potentially be protective. The role of acid-base homeostasis in diabetic CKD progression is complex and must consider differences in endogenous acid production and excretion in diabetes. Ongoing observational and interventional studies in this field should consider the unique physiology of diabetes. 10.1007/s11892-017-0855-6
The role of kidney in glucose homeostasis--SGLT2 inhibitors, a new approach in diabetes treatment. Andrianesis Vasileios,Doupis John Expert review of clinical pharmacology The role of the kidney in blood glucose-level regulation was until recently underestimated. Renal gluconeogenesis, renal glucose uptake and tubular glucose reabsorption are the three ways of renal involvement in glucose homeostasis. In the postabsorptive state, 20% of total glucose release is attributed to renal gluconeogenesis. Tubular glucose reabsorption is performed by the combined action of Na⁺/D-glucose SGLTs co-transporters and GLUT-facilitated diffusion glucose transporters. SGLT2 inhibitors are a new family of agents, which occlude the path of SGLT2 glucose reabsorption and cause glucosuria. Efficacy of SGLT2 inhibitors includes reduction of HbA1c, fasting and postprandial blood glucose level and slight body weight and systolic blood pressure decrease. The most common adverse events of them are genital mycotic and urinary tract infections. Dapagliflozin and canagliflozin are the first agents of this class, approved from the European Medicine Agency and FDA, respectively. 10.1586/17512433.2013.827399
[Sodium-glucose cotransporter type 2 inhibitors (SGLT2): from familial renal glucosuria to the treatment of type 2 diabetes mellitus]. Pérez López G,González Albarrán O,Cano Megías M Nefrologia : publicacion oficial de la Sociedad Espanola Nefrologia For centuries, the kidney has been considered primarily an organ of elimination and a regulator of salt and ion balance. Although once thought that the kidney was the structural cause of diabetes, which in recent years has been ignored as a regulator of glucose homeostasis, is now recognized as a major player in the field of metabolic regulation carbohydrate. During fasting, 55% of the glucose comes from gluconeogenesis. Only 2 organs have this capability: the liver and kidney. The latter is responsible for 20% of total glucose production and 40% of that produced by gluconeogenesis. Today we have a better understanding of the physiology of renal glucose transport via specific transporters, such as type 2 sodium-glucose cotransporter  (SGLT2). A natural compound, phlorizin, was isolated in early 1800 and for decades played an important role in diabetes and renal physiology research. Finally, at the nexus of these findings mentioned above, recognized the effect of phlorizin-like compounds in the renal glucose transporter, which has offered a new mechanism to treat hyperglycemia. This has led to the development of several potentially effective treatment modalities for the treatment of diabetes. 10.3265/Nefrologia.pre2010.Sep.10494
Renal epidermal growth factor receptor: its role in sodium and water homeostasis in diabetic nephropathy. Panchapakesan Usha,Pollock Carol,Saad Sonia Clinical and experimental pharmacology & physiology 1. Volume expansion is observed in animal and human models of diabetic nephropathy, which is in a large part a result of disordered renal tubular cell sodium and water transport. 2. Sodium transport in the proximal tubule is increased in diabetes mellitus as a result of enhanced activity of the sodium-hydrogen exchanger-3 (NHE3), the key transporter for transcellular reabsorption of sodium. Transactivation of the epidermal growth factor receptor (EGFR) by factors inherent in the milieu of diabetes mellitus increases serum glucocorticoid regulated kinase-1 (Sgk1), a key regulator of NHE3. 3. Enhanced sodium and water reabsorption, occurring as a consequence of endogenous or pharmacological stimulation of the peroxisome proliferator-activated receptor gamma is Sgk1 mediated. 4. EGFR inhibitors, which are currently used clinically to treat malignancies, might have potential in attenuating the cellular mechanisms responsible for thiazolidinedione (TZD)-mediated sodium and water transport in diabetes. 5. In the present review, the authors focus on the importance of the EGFR in sodium and water uptake in the proximal tubule in the environment of pathophysiological and pharmacological influences. 10.1111/j.1440-1681.2010.05472.x
Metabolism and homeostasis in the kidney: metabolic regulation through insulin signaling in the kidney. Kuczkowski Alexander,Brinkkoetter Paul T Cell and tissue research Metabolic signaling pathways orchestrate the dynamic turnover between catabolic and anabolic processes. Thereby, they ensure the viability of the cell and assure proper function of the tissue in changing environments regarding the availability of nutrients. Yet, renal cells are not considered to be prime targets of metabolic signaling. Research of the last decade has proposed new roles of specifically altered metabolic signaling pathways. In particular, the insulin signaling cascade, a potent regulator of cellular metabolism and energy homeostasis, seems to be implicated in the progression of diabetic and non-diabetic kidney disease. The aim of this review is to summarize the current knowledge on metabolic signaling events in different renal compartments in states of health and disease. We will focus on the role of insulin signaling events and highlight recent advances in the understanding of the regulatory interplay between insulin signaling and mitochondrial function contributing to the pathogenesis of kidney disease. 10.1007/s00441-017-2619-7
Glucose Homeostasis and Cardiovascular Alterations in Diabetes. Xiang Lusha,Mittwede Peter N,Clemmer John S Comprehensive Physiology Diabetes mellitus is an increasingly prevalent disease associated with a high morbidity and mortality burden. Many of the adverse outcomes secondary to diabetes occur as a result of the impaired glucose homeostasis and pathophysiological alterations to the cardiovascular system. The purpose of this overview is to broadly discuss many of the changes that occur in the context of diabetes that affect cardiovascular function. Following a brief introduction to the classification and etiologies of the various forms of diabetes, the mechanisms of impaired glucose homeostasis will be covered. Vascular endothelial dysfunction, which has been posited to play a major role in the development of target organ pathology, will be addressed, followed by a discussion of the effects of diabetes on the renal, cardiovascular, and pulmonary systems. 10.1002/cphy.c150001
Autophagy and Diabetic Nephropathy. Cui Jing,Bai Xueyuan,Chen Xiangmei Advances in experimental medicine and biology In recent years, diabetic kidney disease has been the main cause of end-stage renal disease; more and more people have faced this serious public health problem worldwide. Autophagy is a conserved multistep pathway that degrades and recycles damaged organelles and macromolecules to maintain intracellular homeostasis. Autophagy plays key roles in several diseases, including kidney diseases. It has been suggested that dysregulated autophagy plays a vital role in both glomerular and tubulointerstitial pathologies in kidneys under diabetic conditions. The advances in our understanding of autophagy in diabetic kidney disease will be helpful for us to discover a new therapeutic target for the prevention and treatment of this life-threatening diabetes complication. 10.1007/978-981-15-4272-5_36