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

Abstract

<p>ABSTRACT<br />Objective: Aloe-emodin glycosides (AEG) isolated from Cassia fistula stimulates glucose transport and glycogen storage through a phosphatidylinositol<br />3 kinase (PI3K)-dependent mechanism in L6 myotubes and inhibits adipocytes differentiation in 3T3L1 adipocytes was previously reported. This<br />study intended to investigate the insulin mimetic effect of AEG by in vivo method.<br />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<br />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<br />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<br />with AEG. The carbohydrate metabolism in diabetic rats appeared to improve due to regulation in hepatic enzymes such as hexokinase, glucose-6phosphatase,<br />and fructose<br />1,6-bisphosphatase with a concomitant increase<br />in glycogen<br />content.<br />Results: AEG decreased lipid peroxidation and improved the antioxidant (enzymatic and nonenzymatic) levels in the liver of diabetic rats. Treatment<br />with AEG (30 mg/kg) augmented the phosphorylation of insulin downstream regulators such as insulin receptor beta, insulin receptor substrate 1,<br />PI3K, glucose transporter 4, glycogen synthase kinase 3 beta, and peroxisome proliferator activator receptor gamma in the skeletal muscle tissue of<br />the Type-2 diabetic rats compared to vehicle-treated diabetic rats.<br />Conclusion: The present results suggested that AEG could serve as an interesting candidate in the drug development for the management of diabetes.<br />Keywords: Aloe-emodin glycoside, Type-2 diabetes, High-fat diet/streptozotocin, Carbohydrate Metabolism, Glycogen, Antioxidant enzyme.</p>