Research About Influence Of Ecdysterone On Insulin Sensitivity Of Experimental Type 2 Diabetic Rats And Its Mechanism

PATR ONE Establishment and Evaluation of model of Insulin resistance in type 2 diabetic ratsObjective:To establish rat model of insulin resistance with its feature and pathogenesis of IR similar to T2DM of humanity through high-fat diet and low-dose STZ injection.Method:Male Wistar rats were fed a special high-fat diet for 8 weeks to induce high blood lipids and insulin resistance, then given a small dose of streptozotocin (STZ) by intraperitoneal injection 30mg/kg once only to lead to insulin secretion obstacle and induce high blood sugar and establish the type 2 diabetic rat model.Use High plasma insulin-euglycemic clamp technique (the clamp experiment) to detect insulin sensitivity, determine whether the IR model were successfully reproduced.Result:Compared with the normal diet, high fat diet rats had hyperlipidemia. After a week of STZ injection, its blood glucose had moderately elevated and reached diagnostic criteria for diabetes. The glucose infusion rate (GIR) and insulin sensitivity index (ISI) of high-fat diet groups were both significantly decreased,and the fasting plasma insulin was significantly increased.All of these were suggested that high-fat diet had successfully induced IR of rat.Conclusion:It can successfully replicate the experimental model of type 2 diabetes by high-fat diet combined with low dose STZ injection.And it's a ideal model for research on pathogenesis of type 2 diabetes and insulin resistance-related diseases,because the model has characteristics such as high blood sugar, high blood lipids, insulin resistance and impaired insulin function and so on.PATR TWO Effect of ecdysterone in insulin resistance of experimental type 2 diabetic ratsObjective:To study the effects of ecdysterone on insulin sensitivity of experimental type 2 diabetic rats and its influence on blood lipid and glucose metabolism. Methods:To establish type 2 diabetic rat model through high-fat diet plus low-dose STZ injection, and then treat with ecdysterone, at the same time treat with pioglitazone for contrast. To observe the improvement of insulin resistance and influence on glucose and lipid metabolism effects of each group.Results:Ecdysterone intragastric administration can significantly reduce fasting blood glucose and plasma insulin levels of T2DM·rats, also can regulate blood lipid. Ecdysterone can significantly increased GIR and ISI of type 2 diabetic rats which has no significant difference compared with pioglitazone treatment group (P>0.05).Conclusion:Ecdysterone can significantly improve glucose and lipid metabolism of T2DM rats, also can significantly improve insulin sensitivity of diabetic rats and showed the dose-effect curve.PART THREE Influence of ecdysterone on protein expression and phosphorylation of liver LXRa of experimental type 2 diabetic ratObjective:To observe influence of ecdysterone on the expression and phosphorylation of hepatic LXRa diabetic rat, in order to explore mechanism of improving insulin resistance by ecdysterone through LXRa. Methods:To establish type 2 diabetic rat model, then give ecdysterone orally for 6 weeks compared with pioglitazone treatment. Detect the expression of hepatic LXRa protein of diabetic rat by Western-blot, and sublimate LXRa protein by immunoprecipitation then add the anti-phosphorylated serine antibody to detect the expression of phosphorylation of LXRa.Results:Ecdysterone has no obvious effect on expression of liver LXRa protein of diabetic rat,but ecdysterone has significantly improved the expression of phosphorylation of LXRa protein of diabetic rat. Conclusion:Ecdysterone has no effect on expression of liver LXRαprotein of experimental diabetic rat, but can increased the expression of its phosphorylation. Ecdysterone plays a role in insulin sensitivity by liver x receptor pathway through the promotion of LXRa protein phosphorylation in experimental type 2 diabetic rats, which may be one of the molecular mechanisms of insulin sensitivity.