Michel Barbosa de Araújo

Melatonin prevents mitochondrial dysfunction and insulin resistance in rat skeletal muscle

Melatonin has a number of beneficial metabolic actions and reduced levels of melatonin may contribute to type 2 diabetes. The present study investigated the metabolic pathways involved in the effects of melatonin on mitochondrial function and insulin resistance in rat skeletal muscle. The effect of melatonin was tested both in vitro in isolated rats skeletal muscle cells and in vivo using pinealectomized rats (PNX). Insulin resistance was induced in vitro by treating primary rat skeletal muscle cells with palmitic acid for 24 hr. Insulin‐stimulated glucose uptake was reduced by palmitic acid followed by decreased phosphorylation of AKT which was prevented my melatonin. Palmitic acid reduced mitochondrial respiration, genes involved in mitochondrial biogenesis and the levels of tricarboxylic acid cycle intermediates whereas melatonin counteracted all these parameters in insulin‐resistant cells. Melatonin treatment increases CAMKII and p‐CREB but had no effect on p‐AMPK. Silencing of CREB protein by siRNA reduced mitochondrial respiration mimicking the effect of palmitic acid and prevented melatonin‐induced increase in p‐AKT in palmitic acid‐treated cells. PNX rats exhibited mild glucose intolerance, decreased energy expenditure and decreased p‐AKT, mitochondrial respiration, and p‐CREB and PGC‐1 alpha levels in skeletal muscle which were restored by melatonin treatment in PNX rats. In summary, we showed that melatonin could prevent mitochondrial dysfunction and insulin resistance via activation of CREB‐PGC‐1 alpha pathway. Thus, the present work shows that melatonin play an important role in skeletal muscle mitochondrial function which could explain some of the beneficial effects of melatonin in insulin resistance states.

Effects of Moderate Intensity Physical Training in Neonatal Alloxan- Administered Rats

Newborn rats (6 days old) received alloxan intraperitoneally (A= 250 mg/kg b.w). Rats injected with vehicle (citrate buffer) were used as controls (C). After weaning, half of the animals were submitted to 1 hour/day, 5 days/week swimming and with supporting overload of 5% b.w. At 28 days, no signi fi cant differences were found among the groups in fasting glycemia and insulinemia. At 60 days, the fasting glycemia (30 min after oral glucose administration) was higher in alloxan than in controls groups and lower in the alloxan group submitted to training than in the correspondent sedentary group. The glucose tolerance of the alloxan rats was reduced in comparison to controls, both at 28 and 60 days, since the area under the blood glucose curve during the OGTT was higher in the alloxan than in the control. No difference was found among the groups both at 28 and 60 days in the HOMA index. However, a slight reduction was observed in the values of the trained groups suggesting slightly increased insulin sensitivity in the animals. These results suggest that this diabetes mellitus animal model presents interesting characteristics for the study of the role of the physical exercise in diabetes outcome.

Hepatic Steatosis Markers in Diabetic Rats Trained at the Aerobic/ Anaerobic Transition

Aims: To analyze the effects of exercise performed at the aerobic/anaerobic transition (Lan) on Non-Alcoholic Hepatic Steatosis (NAHS) markers in type 1 diabetic rats. Methods: Adult Wistar rats were separated into four groups: Sedentary Control (SC), Trained Control (TC), Sedentary Diabetic (SD) and Trained Diabetic (TD). The trained groups swam supporting workloads equivalent to the Lan for one hour/day, five days/week, for eight weeks. Body weight, serum albumin concentrations, glucose concentrations, Free Fatty Acid (FFA) concentrations, NAHS markers (Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) and total lipid concentrations in the liver were analyzed. Results: The diabetic groups showed higher serum glucose concentrations and more weight loss compared to the controls, although the TD group was less affected than the SD group. Training resulted in a decrease in serum glucose levels in the diabetic rats. The NAHS markers, total lipid concentrations in the liver and serum albumin concentrations did not differ between the groups. However, the diabetic animals had higher serum FFA levels than the controls. Conclusion: Physical training at Lan attenuates weight loss and improves serum glucose homeostasis in diabetic animals. In addition, serum ALT and AST enzymes proved to be adequate markers of lipid levels in the livers in this animal model.