白藜芦醇对KKAy小鼠的胰岛素敏感性影响及机制

Effect and Mechanism of Resveratrol on Insulin Sensitivity in Insulin-resistant KKAy Mice

目的:观察白藜芦醇对胰岛素抵抗小鼠(KKAy)胰岛素敏感性的影响,并探讨其机制。方法:将36只8周龄KKAy小鼠分成3组,其中两组KKAy小鼠分别饲喂添加白藜芦醇的AIN93G饲料(2g/kg饲料或4g/kg饲料),另一组KKAy小鼠为模型组,另外以12只同周龄C57BL/6J小鼠为对照。观察白藜芦醇对小鼠血糖、血清胰岛素水平、葡萄糖耐量、胰岛素耐量等的影响;Western blot实验检测不同组小鼠肝脏中沉默信息调节因子1(silent in-formation regulator 1,sirt-1)蛋白表达及胰岛素受体底物1(insulin receptor substrate 1,IRS-1)的磷酸化水平。结果:白藜芦醇干预可以增强KKAy小鼠胰岛素敏感性,改善胰岛素耐量和葡萄糖耐量;肝脏中sirt-1的表达和IRS-1的磷酸化水平均升高。结论:白藜芦醇可以改善小鼠胰岛素抵抗及糖耐量异常,这可能与白藜芦醇提高肝脏中sirt-1的表达,从而激活胰岛素信号通路相关蛋白有关。

Objective：To investigate the effect of resveratrol on insulin sensitivity in insulin-resistant KKAy mice and to probe the mechanism.Methods：A total of 36 7-week-old KKAy mice were randomly divided into 3 groups,which were fed standard AIN93G diet or standard AIN93G diet with resveratrol at contents of 2 g/kg and 4 g/kg diet.Totally 12 C57BL/6J mice were used as the control.The 12 h fasting levels of blood glucose and serum insulin and glucose and insulin tolerance at 0,6 weeks and 12 weeks of drug intervention were determined to evaluate the effect of resveratrol.The expression of silent information regulator（sirt-1） and phosphorylation of insulin receptor substrate 1（IRS-1） in liver were examined by western blotting.Results：Resveratrol significantly improved insulin sensitivity of KKAy mice,ameliorated glucose tolerance and insulin tolerance,and enhanced the expression level of sirt-1 and phosphorylation of IRS-1 in liver.Conclusion：Resveratol may ameliorate insulin resistance and glucose tolerance disorder of mice due to its promotion effect on the expression of sirt-1 in liver and activation effect on the proteins related to insulin signaling.