Molecular Mechanism Of Berberine On Improving Glucose Metabolic Disorder In Insulin Resistant Rats

Part 1 Assessment of the feasibility of inducing murine model of insulin resistance by feeding high-fat forageObjective: To study the feasibility of using high polyunsaturated fat forage to feed Wistar rats to induce murine insulin resistant model.Methods: Wistar rats were fed with high-fat forage for 8 weeks. The murine serum TG, TC were measured. Glucose tolerance test and insulin releasing test on experimental animals were performed, and the insulin sensitivity index, area under curve of glucose tolerance test and area under curve of insulin releasing test were therefore calculated.Results: As compared with control group, the animal fasting serum TG in model group after 8-week feeding showed no statistic change (P>0.05), while serum TC and Fins levels in model group were evidently increased (P<0.01); the ISI decreased significantly (P<0.01) and the AUCIns in model group was significantly larger than that in control group (P<0.01).Conclusion: The ISI of high-fat-fed group was lower and modeled rats suffered from insulin resistance syndrome, which confirmed that the method of using high-fat forage to feed rats to induce insulin resistant model is feasible. Part 2 The effect of berberine on glucose metabolism to insulin resistant ratsObjective: To investigate whether berberine can improve insulin resistance by using berberine to treat insulin resistant rats.Methods: After insulin resistant model was induced, berberine was used to treat rats for 4 weeks, then the murine fasting serum TG, TC, FFA were measured, and GTT and IRT were performed to calculate ISI, AUCBG, AUCIns and etc.Results: Compared with model group, the fasting serums TG and TC in berberine group were mildly lower, but without statistic significance (P>0.05); FFA in berberine group was significantly lower (P<0.05); the ISI was higher in berberine group (P<0.05); The curve of insulin releasing was smoother and the AUCBG was smaller in berberine group than that in model group (P<0.05).Conclusion: Berberine might improve insulin resistance and strengthen the insulin sensitivity on insulin resistant rats. Part 3 Effect of berberine on glucokinase and glucokinase regulatory protein of insulin resistant ratsObjective: To study the effect of berberine on hepatic glucokinase activity, protein expressions of hepatic and pancreatic glucokinase and glucokinase regulatory protein in insulin resistant rats, and to reveal the molecular mechanism of berberine regulating glucose metabolism and improving insulin resistance.Methods: Berberine was administrated to treat insulin resistant rats for 4 weeks, then the enzymic activity of hepatic glucokinase was measured. The protein expressions of hepatic and pancreatic glucokinase and glucokinase regulatory protein were determined.Results: Compared with model group, the hepatic glycogen level evidently enhanced (P<0.05); the enzymic activity of glucokinase of berberine group was significantly strengthened (P<0.05); the protein expression of hepatic glucokinase was elevated (P<0.05) in berberine group. There was no significant change of the pancreatic glucokinase protein in berberine group (P>0.05), while the protein expressions of hepatic and pancreatic glucokinase regulatory protein in berberine group were all significantly declined in berberine group (P<0.05).Conclusion: The mechanism of berberine regulating glucose metabolism and improving insulin resistance might be related with its strengthening effects on the enzymic activity of glucokinase.