Chebulagic acid attenuates HFD/streptozotocin induced impaired glucose metabolism and insulin resistance via up regulations of PPAR γ and GLUT 4 in type 2 diabetic rats

Abstract

The aim of the present study was to evaluate the effects of chebulagic acid on enzymes involved in carbohydrate metabolism in high-fat diet/streptozotocin-induced diabetic rats. Diabetes was induced in albino male Wistar rats by feeding them with a high-fat diet comprising of 84.3% standard laboratory rat chow, 5% lard, 10% yolk powder, 0.2% cholesterol, and 5% bile salt for 2 weeks. After 2 weeks, the animals were kept in an overnight fast and injected with a low dose of streptozotocin (35 mg/kg, dissolved in 0.1 M sodium citrate buffer, pH 4.5). At the end of the experimental periods, the blood glucose, plasma insulin, hemoglobin, glycated hemoglobin levels, homeostatic model of insulin resistance, glycogen content, glycogen synthase, glycogen phosphorylase were measured in high-fat diet and streptozotocin-induced diabetic rats whereas the glucose metabolic enzymes such as hexokinase, glucose 6 phosphate dehydrogenase, glucose 6 phosphatase, fructose 1,6 bisphosphatase and protein expression of peroxisome proliferator-activated receptor–γ (PPAR-γ) and Glucose transporter 4 (GLUT4) were analyzed. Administration of chebulagic acid to HFD/STZ -induced diabetic rats for 30 days significantly decreased the levels of plasma glucose, homeostatic model assessment of insulin resistance, glycogen phosphorylase and glycosylated hemoglobin and increased the levels of insulin, glycogen content and glycogen synthase. On the other hand, the altered activity of carbohydrate metabolic enzymes, PPAR-γ and GLUT4 were brought back to near-normal levels on treatment with chebulagic acid. The effect produced by chebulagic acid on various parameters was comparable to that of metformin.