Effects And Mechanisms Of Rhein On Improvement Of Insulin Sensitivity Of Diabetic Rats

Objective To investigate the effects and mechanisms of rhein on improvement of insulin sensitivity of diabetic rats through increasing expression levels of PPARy and GLUT-4 in adipose tissue.Methods Male Wistar rats were randomly divided into normal control group (NC, n=15) and diabetic group (DM, n=40). The diabetic model was set up by injecting a low dose of streptozotocin (STZ, 30 mg/kg) once after feeding high-fat diet for 5 weeks. The rats with fasting blood glucose (FBG) higher than 11.1 mmol/l were selected to be the diabetic model (n=30). These rats were randomly divided into diabetic control group (DM-C, n=15) and diabetic group treated with rhein (DM-T, n=15). Then DM-T group was given intragastric administration with rhein at the dose of 100 mg/ (kg·d) for 11 weeks. FBG, fasting serum insulin (FIN), triglyceride (TG), total cholesterol (TC), insulin sensitivity index (IAI) and other biochemical parameters in each group were measured. Expression levels of peroxisome proliferator activated receptor y (PPARy) and glucose transporter 4 (GLUT-4) were determined by immunohistochemistry and western blot, respectively.Results The rat model of diabetes mellitus was set up successfully. At the end of the 17th weeks, that was the end of the 11th weeks of rhein treatment, compared with NC group, DM-C group got much higher FBG[(22.57±3.23 vs 7.45±1.81) mmol/l, P<0.01], lower IAI (-5.46±0.61 vs -4.81±0.75, P<0.05), higher TG [(0.89±0.29 vs 0.58±0.17) mmol/l, P<0.01]. Integrated optical density showed much lower expression level of PPARy protein of DM-C group in adipose tissue than that of NC group [4750.70(3346.63-10390.63) vs 9986.85 (6599.68 -14655.60), P<0.01]. Integrated density showed lower expression level of GLUT-4 protein of DM-C group in adipose tissue than that of NC group [0.828(0.621-1.010) vs 1.640(1.186-1.948), P<0.01]. Compared with DM-C group, DM-T group got lower FBG [(15.73±3.08 vs 22.57±3.23) mmol/l, P<0.01], higher IAI (-4.97±0.29 vs -5.46±0.61, P<0.05). Integrated optical density showed higher expression level of PPARy protein of DM-T group in adipose tissue than that of DM-C group [13613.35 (7293.85-17198.73) vs 4750.70 (3346.63-10390.63), P<0.01]. Integrated density showed higher expression level of GLUT-4 of DM-T group in adipose tissue than that of DM-C group [1.157 (0.921-1.953) vs 0.828 (0.621-1.010),P<0.01].Conclusions 1. Rhein decreases FBG and improves insulin sensitivity ofdiabetic rats.2. Increasing expression levels of PPARy and GLUT-4 in adipose tissue may be one of mechanisms of rhein's improving insulin sensitivity.