A Study On Possible Mechanism Of Leptin Improves Glucose And Lipids Metabolism In Type 2 Diabetic Ob/ob Mice

objective The present study aimed to investigate the improvement of leptin on weight, glucose and lipids metabolism,and exploring its possible mechanism from oxidative stress, endoplasmic reticulum stress and insulin resistance. Methods Choosing leptin-deficient ob/ob mice as animal model of type 2 diabetes mellitus, treating with or without leptin respectively(1mg/kg/day, intraperitoneal injection), choosing C57BL/6J wild-type mice for control group, and recording daily weight. Using Roche ACCU-CHEK? to measure blood glucose; detecting serum triglyceride(TG) and cholesterol(TC) which reflected lipids metabolism, and serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) which reflected liver function; measuring the serum level of insulin with Elisa; detecting the protein expression level of Indicators of oxidative stress- NOX4, antioxidative enzyme- CAT,,endoplasmic reticulum stress symbol- GRP78, AKT-Fox O1 activation and Pepck protein expression in the classical pathway of glucose and lipids metabolism regulated by insulin,and key molecules m TOR activation in Insulin regulation of lipid metabolism pathway and the protein levels of Srebp1 related in lipid synthesis with western blot. Results Compared with wild-type mice, the weight, blood glucose, serum TG and TC, serum ALT and AST activity, and serum insulin level of ob/ob mice were increasing significantly; compared with ob/ob mice, the weight, blood glucose, serum TG and TC, serum ALT and AST activity, and serum insulin level of ob/ob mice treated with leptin were decreasing significantly. Compared with wild-type mice, there were significantly increasing protein expression level of liver NOX4 and GRP78, and decreasing protein expression level of CAT in ob/ob mice; compared with ob/ob mice, there were significantly decreasing protein expression level of liver NOX4 and GRP78, and increasing protein expression level of CAT in ob/ob mice treated with leptin. Compared with wild-type mice, the liver p-AKT and p-Fox O1 of ob/ob mice were decreasing significantly; compared with ob/ob mice, the liver p-AKT and p-Fox O1 of ob/ob mice dealed with leptin were increasing significantly; Compared with wild-type mice, the liver p-m TOR and protein expression of Srebp1 were increasing significantly; compared with ob/ob mice, the liver p-m TOR and Srebp1 decreasing significantly. Conclusion Leptin could reduce the weight, improve the glucose and lipids metabolism and liver function of type 2 diabetic mice singnificantly, which might related to the mechanism of leptin reducing liver oxidative stress and endoplasmic reticulum stress, and restoring sensitivity to insulin.