Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus

Abstract Introduction The objective was to investigate the effects of melatonin and exercise on insulin resistance (IR), hypertension and fatigue syndrome in a rat model of type 2 diabetes mellitus (T2DM). Materials and methods Rats were divided into 5 groups namely normal control (NC), T2DM control group (DC), diabetes plus exercise (DE), diabetes plus oral melatonin supplement (DM) and diabetes plus melatonin and exercise (DME) groups. Melatonin was administered orally 5 mg/kg twice daily and 40 min swimming/day 5 days/week were regimented after diabetes induction. Results Blood pressure, fasting blood glucose, insulin, IR, serum leptin, lipid profiles, inflammatory cytokines, lipid peroxidation increased significantly (P < 0.01) while serum adiponectin, antioxidant activities (superoxide dismutase, glutathione), exercise performance significantly decreased (P < 0.001) in the DC group compared with the control group. Combined effects of exercise and melatonin ameliorated markedly hypertension, IR, biochemical alteration induced by diabetes and significantly increased exercise performance (P < 0.01). The expression glucose transporter type 4 (GLUT4) mitochondrial biogenesis related proteins such as peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1 α), nuclear respiratory factor (NRFs) and mitochondrial transcription factor-A were up-regulated skeletal and cardiac muscle in the DME group. Conclusion Melatonin supplementation in combination with exercise behavior may ameliorate IR, hypertension and exercise performance or fatigue possibly by improving antioxidative activities, hyperlipidemia, inflammatory cytokines via up-regulation of GLUT4, PGC-1 α and mitochondrial biogenesis in T2DM rats.