IRS-1的表达和泛素化在KKAy及C57BL/6J小鼠糖尿病发展过程中的意义

目的:探讨胰岛素受体底物-1(IRS-1)蛋白表达和泛素化水平在糖尿病发展过程中的作用。方法:20只8周龄C57BL/6J小鼠随机分为正常对照组(正常饲料喂养,n=10)和胰岛素抵抗组(高脂饲料喂养,n=10)。8周龄KKAy小鼠8只,高脂饲料喂养,为2型糖尿病组。检测各组小鼠体重、血糖和血胰岛素水平。12周后免疫印迹检测各组动物肝组织IRS-1的表达量,同时采用剥离免疫印迹法检测肝组织IRS-1的泛素化水平。结果:高脂喂养12周后C57BL/6J小鼠出现胰岛素抵抗,KKAy小鼠出现肥胖和糖尿病。2型糖尿病组IRS-1的表达显著低于正常对照组和胰岛素抵抗组(P<0.05),而IRS-1的泛素化水平则显著高于胰岛素抵抗组(P<0.05),与对照组无显著性差异(P>0.05)。结论:2型糖尿病时IRS-1的表达下调,IRS-1泛素化水平增加是导致胰岛素信号转导障碍的重要原因。

Effects of Expression and Ubiquitylation of IRS-1 During the Development of Diabetes in KKAy Mice and C57BL/6J Mice

Objective: To investigate the effect of expression and ubiquitylation of insulin receptor substrate-1 in the development of diabetes.Methods: Twenty C57BL/6J mice were divided into normal control group(on normal diet,n=10) and insulin resistance group(on high fat/glucose diet,n=10) and diabetes group(eight KKAy mice).The body weight,blood glucose level and plasma insulin concentration of all the mice were measured.After 12 weeks, Western blot and stripping immunoblots were respectively applied to detect the expression levels of IRS-1 and ubiquitin.(Results:) Having been fed with high fat diet for 12 weeks,C57BL/6J mice exhibited the symptoms of insulin resistance.KKAy mice showed the appearance of obesity and the symptoms of type 2 diabetes mellitus.The expression of IRS-1 of type 2 diabetes group was markedly lower than control group and IR group(P<0.05);however,the ubiquitylation level of IRS-1 in DM group is significantly higher than that in IR group(P<0.05),there was no distinct difference between DM group and control group(P>0.05).Conclusion: The expression of IRS-1 is markedly down-regulated in type 2 diabetes,and the enhancement of the ubiquitylation level of IRS-1 contribute to the disorder in insulin signal transferring.