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

摘要

Objective: Aloe-emodin glycosides (AEG) isolated from Cassia fistula stimulates glucose transport and glycogen storage through a phosphatidylinositol 3 kinase (PI3K)-dependent mechanism in L6 myotubes and inhibits adipocytes differentiation in 3T3L1 adipocytes was previously reported. This study 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 were injected 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 and high dose: 30 mg/kg for a period of 21-day. A dose-dependent decrease in fasting blood glucose, cholesterol, and triglycerides levels on treatment with AEG. The carbohydrate metabolism in diabetic rats appeared to improve due to regulation in hepatic enzymes such as hexokinase, glucose-6phosphatase, and fructose 1,6-bisphosphatase with a concomitant increase in glycogen content. Results: AEG decreased lipid peroxidation and improved the antioxidant (enzymatic and nonenzymatic) levels in the liver of diabetic rats. Treatment with 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 of the 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.