ALOE-EMODIN GLYCOSIDES AMELIORATE GLUCOSE UTILIZATION VIA INSULIN DOWNSTREAM REGULATORS: AN IN VIVO INVESTIGATION

Abstract

ABSTRACTObjective: Aloe-emodin glycosides (AEG) isolated from Cassia fistula stimulates glucose transport and glycogen storage through a phosphatidylinositol3 kinase (PI3K)-dependent mechanism in L6 myotubes and inhibits adipocytes differentiation in 3T3L1 adipocytes was previously reported. Thisstudy intended to investigate the insulin mimetic effect of AEG by in vivo method.Methods: Male Wistar albino rats were randomly allocated into two groups and fed for a period of 3-week. The high-fat diet group animals wereinjected with a low dose (35 mg/kg) of streptozotocin to induce Type-2 diabetes. The diabetic rats were then treated with low dose: 10 mg/kg andhigh dose: 30 mg/kg for a period of 21-day. A dose-dependent decrease in fasting blood glucose, cholesterol, and triglycerides levels on treatmentwith AEG. The carbohydrate metabolism in diabetic rats appeared to improve due to regulation in hepatic enzymes such as hexokinase, glucose-6phosphatase,and fructose1,6-bisphosphatase with a concomitant increasein glycogencontent.Results: AEG decreased lipid peroxidation and improved the antioxidant (enzymatic and nonenzymatic) levels in the liver of diabetic rats. Treatmentwith AEG (30 mg/kg) augmented the phosphorylation of insulin downstream regulators such as insulin receptor beta, insulin receptor substrate 1,PI3K, glucose transporter 4, glycogen synthase kinase 3 beta, and peroxisome proliferator activator receptor gamma in the skeletal muscle tissue ofthe Type-2 diabetic rats compared to vehicle-treated diabetic rats.Conclusion: The present results suggested that AEG could serve as an interesting candidate in the drug development for the management of diabetes.Keywords: Aloe-emodin glycoside, Type-2 diabetes, High-fat diet/streptozotocin, Carbohydrate Metabolism, Glycogen, Antioxidant enzyme

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