Effect of pinealectomy on plasma levels of insulin and leptin and on hepatic lipids in type 2 diabetic rats.
Nishida Shigeru,Sato Ryuichiro,Murai Ichiro,Nakagawa Shigeki
Journal of pineal research
We previously reported that pharmacological melatonin administration to type 2 diabetic rats reduces hyperinsulinemia and improves the altered fatty-acid metabolism. To determine whether melatonin deficiency exacerbates diabetes-associated conditions, we investigated the effect of pinealectomy (i.e. melatonin-deficiency) on plasma hormone levels and lipid metabolism in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. We compared levels of insulin and leptin, and hepatic lipids in pinealectomized OLETF (PO) rats, sham-operated OLETF (SO) rats and sham-operated healthy Long-Evans Tokushima Otsuka (LETO) (SL) rats 16 and 30 wk after the operation. Plasma glucose and triglycerides were increased in SO and PO rats 30 wk after operation compared with age-matched SL rats. Pinealectomy caused an increase in free cholesterol among the plasma lipids, as compared with SO rats. Sixteen weeks after pinealectomy, typical hyperinsulinemia was observed in PO rats (3.47-fold increase, P < 0.01) as compared with SL rats, whereas at 30 wk, the plasma levels of insulin in PO and SO rats had decreased and there was no significant difference among the three groups. Hepatic triglycerides were increased (1.54-fold, P < 0.005) in PO rats, compared with SO rats. Hepatic acyl-CoA synthetase (ACS) activity was significantly augmented in PO rats at 30 wk (10%, P < 0.01 versus SO group), while microsomal triglyceride transfer protein (MTP) decreased (-27% versus SO, P < 0.05); thus, the increased ACS activity and decreased MTP might have a role in the accumulation of hepatic triglycerides in PO rats. In summary, pinealectomy causes severe hyperinsulinemia and accumulation of triglycerides in the liver, probably owing to the loss of the nocturnal melatonin surge.
Pinealectomy reduces hepatic and muscular glycogen content and attenuates aerobic power adaptability in trained rats.
Borges-Silva Cristina das Neves,Takada Julie,Alonso-Vale Maria Isabel Cardoso,Peres Sidney B,Fonseca-Alaniz Miriam H,Andreotti Sandra,Cipolla-Neto Jose,Pithon-Curi Tania C,Lima Fabio Bessa
Journal of pineal research
The current study emphasizes the crucial role of the pineal gland on the effects of chronic training in different tissues focusing on carbohydrate metabolism. We investigated the maximal oxygen uptake (aerobic power), muscle and liver glycogen content, and also the enzymes involved in the carbohydrate metabolism of rat adipose tissue. Pinealectomized and sham-operated adult male Wistar rats were distributed into four groups: pinealectomized (PINX) untrained, pinealectomized trained, control untrained and control trained. The maximal oxygen uptake capability was assayed before and after the training protocol by indirect open circuit calorimetry. The rats were killed after 8 wk of training. Blood samples were collected for glucose and insulin determinations. The glycogen content was assayed in the liver and muscle. Maximal activities of epididymal adipose tissue enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase and malic enzyme) as well as adipocyte size were determined. The exercise training in control animals promoted an increase in the aerobic power and in liver glycogen content but caused a reduction in the malic enzyme activity in adipose tissue. However, PINX trained animals, in contrast to trained controls, showed a decrease in the aerobic power and in liver and muscle glycogen content, as well as an increase in the activity of the adipocyte enzymes involved in carbohydrate metabolism. In conclusion, these data show that the pineal gland integrity is necessary for the homeostatic control of energy metabolism among adipose, muscle and hepatic tissues. The pinealectomized animals showed alterations in adaptive responses of the maximal oxygen uptake to training. Therefore, the pineal gland must be considered an influential participant in the complex adaptation to exercise and is involved in the improvement of endurance capacity.
Effects of pinealectomy and exogenous melatonin on the brains, testes, duodena and stomachs of rats.
Tasdemir S,Samdanci E,Parlakpinar H,Polat A,Tasdemir C,Cengiz N,Sapmaz H,Acet A
European review for medical and pharmacological sciences
BACKGROUND:It is generally agreed that physiological levels of melatonin, a hormone secreted by the pineal gland, are important in protecting against oxidative stress-induced tissue damage. AIM:We investigated the effects that pinealectomy and the administration of exogenous melatonin have on the brains, testes, duodena and stomachs of rats. MATERIALS AND METHODS:Pinealectomized (Px) and sham-operated (non-Px) rats were used. We evaluated structural changes, and catalase (CAT), reduced glutathione (GSH), super oxide dismutase (SOD) and malondialdehyde (MDA) levels. The rats were divided into the following five groups (eight rats in each group): sham (non-Px), Px+ vehicle, Px+ melatonin (10 mg/kg given daily intraperitoneally for a week), melatonin and ethyl alcohol. RESULTS:The antioxidant levels in the tissue of Px rats were significantly lower than in those of the sham group. Administering melatonin significantly increased antioxidant levels (p < 0.05). The Px rats also showed a significant increase in MDA levels when compared to the sham group, and administering melatonin to the Px rats significantly reduced their MDA levels (p < 0.05). The severity of caspase-3 staining was lower in the Px+ melatonin group than in the Px+vehicle group. CONCLUSIONS:These findings suggest that significantly more oxidative and structural changes occur in rats' brains, spinal cords and testes after pinealectomy, but that this can be diminished by melatonin treatment. However, Px does not have important effects on the duodenum and stomach.
Melatonin promotes reduction in TNF levels and improves the lipid profile and insulin sensitivity in pinealectomized rats with periodontal disease.
Santos Rodrigo Martins Dos,Marani Fernando,Chiba Fernando Yamamoto,Mattera Maria Sara de Lima Coutinho,Tsosura Thais Verônica Saori,Tessarin Gestter Willian Lattari,Pereira Renato Felipe,Belardi Bianca Elvira,Pinheiro Beatriz Costa E Silva,Sumida Doris Hissako
AIM:This study aimed to investigate the effects of melatonin (ME) on insulin resistance (IR) and signaling (IS), proinflammatory cytokine levels, and lipid profiles in pinealectomyzed (PNX) rats with periodontal disease (PD). MAIN METHODS:One hundred and forty-four rats (age = 40 days) were distributed into 8 groups: 1) control (CN); 2) PD only; 3) PNX only; 4) PNX and PD (PNXPD); 5) CN treated with ME (CNM); 6) PD treated with ME (PDM); 7) PNX treated with ME(PNXM); 8) PNX and PD treated with ME(PNXPDM). The PNX groups were subjected to pinealectomy at 40 and at 60 days of age. The animals were then subjected to PD induction in the mandibular first molars. After PD induction, the ME replacement therapy (MERT-5 mg/kg body weight) was performed using water for 28 days. After this period, the plasma concentration of glucose, insulin, TNF, IL-6, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, and VLDL-cholesterol and the HOMA-IR index were determined. Akt serine phosphorylation status in the white adipose tissue, gastrocnemius muscle, and rat liver were also evaluated. KEY FINDINGS:PD, PNX, and PNXPD groups showed an increase in IR with elevated plasma levels of insulin and TNF compared to CN group. PNX and PNXPD groups presented alteration in lipid profile compared to CN group. MERT improved all of the analyzed parameters. No difference was observed in the IS among different groups. SIGNIFICANCE:The results suggest that MERT efficiently prevents IR, improves lipid profile, and increases plasma levels of insulin and TNF in PD and PNX rats.
Effect of endurance training on diurnal rhythms of superoxide dismutase activity, glutathione and lipid peroxidation in plasma of pinealectomized rats.
Jana Tchekalarova,Tzveta Stoyanova,Zlatina Nenchovska,Natasha Ivanova,Dimitrinka Atanasova,Milena Atanasova,Katerina Georgieva
Melatonin deficit is characterized by disturbed circadian rhythms of many physiological and biochemical parameters including markers of oxidative stress. Moderate endurance training exerts protection against oxidative stress. In the present study, we aimed to explore the impact of endurance treadmill training on disturbed rhythmic fluctuations of some markers of oxidative stress in pinealectomized rats. Animals were divided into four groups: sham-operated sedentary rats (sham-sed), a sham group with exercise (sham-ex), pinealectomized sedentary rats (pin-sed) and pin rats with exercise (pin-ex). Animals were sacrificed by decapitation at 4-h intervals for biochemical analysis of plasma melatonin and markers of oxidative stress. The activity of superoxide dismutase (SOD) and the levels of glutathione (GSH) and lipid peroxidation demonstrated diurnal variations in the sham-sed group. The peak values of SOD were detected during the dark period that coincided with the peak plasma levels of melatonin in the sham-sed rats. The malondialdehyde (MDA) levels also showed a tendency to a progressive raise during the dark period. Pinealectomy was characterized by a remarkable melatonin deficit in plasma of sedentary rats, compromised fluctuations with decreased SOD activity and increased lipid peroxidation. While endurance training was unable to restore the melatonin deficit, it partly prevented the oxidative stress at selected time points in the pinealectomised rats. Our findings indicate the important role of endurance training against oxidative stress both in physiological conditions and melatonin deficit.