二甲双胍对OLETF大鼠靶组织内胰岛素受体底物-1蛋白表达水平的影响

目的探讨二甲双胍作用的分子机制。方法用Western杂交检测二甲双胍治疗后自发发病的2型糖尿病模型(OLETF大鼠)肝脏、肌肉、脂肪组织内IRS-1(胰岛素受体底物1)蛋白表达水平的改变，并与治疗前比较。结果二甲双胍治疗后OLETF大鼠肝脏组织内IRS-1的蛋白表达较治疗前明显增加(P＜0.001)，肌肉组织内IRS-1的蛋白表达亦较治疗前增加，但差别无统计学意义(P＞0.05)，脂肪组织内IRS-1的蛋白表达则较治疗前减少(P＜0.05)。结论二甲双胍治疗后能使OLETF大鼠靶组织内IRS-1蛋白表达发生改变，特别是它能明显增加肝脏组织IRS-1的蛋白表达，这可能是其抗高血糖、改善组织胰岛素敏感性的机制之一。

Influence of metformin on the protein expression of IRS-1 in target tissues of OLETF rats

Objective To investigate the molecular mechanism of metformin. Methods The changes of protein expression of IRS-1 in liver, skeletal muscle and adipose tissues after treatment with metformin for OLETF rats, a model of spontaneous type 2 diabetes mellitus, were measured by Western blot analysis, and compared with those before treatment. Results 22 weeks after the treatment with metformin, the protein expression of IRS-1 was significantly increased in liver (P<0.001);the protein expression of IRS-1 in skeletal muscle had also a increase compared with that of controls,but the difference was not statistically significant (P>0. 05) ;and the protein expression of IRS-1 in adipose tissue was significantly decreased (P<0.05). Conclusion Administration of metformin result in altering expression of IRS-1 protein in target tissues; Particularly, it could markedly increase expression of IRS-1 protein in liver tissue,which may be one of the molecule mechanism that improves insulin sensitivity of target tissues.