mTOR/S6K1信号通路在高脂饮食诱导小鼠胰岛素抵抗发生中的作用  

The effect of mTOR/S6Kl signaling pathway on the development of high fat diet-induced mouse insulin resistance

作　　者：苑红[1,2] 牛燕媚[1] 刘彦辉[1] 苏照鹏[1] 李慧阁[1] 傅力[1] 

机构地区：[1]天津体育学院健康与运动科学系,300381 [2]内蒙古医学院生物化学与分子生物学教研室工作

出　　处：《中国糖尿病杂志》2009年第12期884-888,共5页Chinese Journal of Diabetes

基　　金：国家自然科学基金资助项目(30871213);天津市科委应用基础及前沿技术重点研究计划(09JCZDJC17400);天津市重大攻关资助项目(05YFGDSF02100)

摘　　要：目的探讨mTOR及其下游效应因子S6K1在胰岛素抵抗(IR)发生中的作用。方法C57BL/6雄性小鼠20只随机平均分为正常饮食组(NC组)和高脂饮食组(HF组)。后者喂养14周后建立IR模型。检测两组血清胰岛素水平和葡萄糖耐量,显微镜下观察胰岛形态学变化;检测骨骼肌中mTOR和S6K1 mRNA的表达,以及mTOR、S6K1和其磷酸化水平蛋白的表达。结果与NC组相比,HF组小鼠表现出明显的IR症状,其体重和空腹胰岛素分别升高了21.99%(P<0.05)和181.82%(P<0.01);胰岛β细胞团面积也显著增加,糖耐量明显受损,骨骼肌细胞中mTOR mRNA和蛋白分别升高了25.61%(P<0.05)和37.41%(P<0.01),S6K1 mRNA和蛋白分别升高了54.98%(P<0.01)和37.36%(P<0.01),S6K1磷酸化水平蛋白表达在高脂饮食后升高了680.15%(P<0.01)。结论mTOR/S6K1信号通路与高脂饮食诱导IR的发生密切相关。Objective To investigate the effects of mTOR/S6K1 signaling pathway on the development of insulin resistantce. Methods 20 male C57BL/6 mice were divided into normal diet group （NC） and high fat diet group （HF）. HF mice were fed with high fat diet for 14 weeks and insulin resistance was confirmed in all mice. We observed the morphology of pancreatic islet by HE staining. Serum insulin concentration was also evaluated by ELISA. Northern blot, Western blot and immunofluorescence were performed to detect mTOR and S6K1 mRNA and protein ＇expression in skeletal muscle. Results As compared with NC group, HF group showed that the body weight and fasting serum insulin level were increased by 21.99% （P〈0. 05） and 181.82% （P〈0. 01） respectively; the area of pancreatic islet was significantly increased; glucose tolerance was impaired; expressions of roTOR mRNA （125.61± 10.43 vs 100.00, P〈0.05） and protein （137.41 ±7.86 vs 100.00, P〈0.01） were significantly increased. And we also found an significant increase in total S6K1 mRNA （154.98±16.26 vs 100. 00, P〈0. 01） and protein （137.36±3.08 vs 100.00,P〈0.01） as well as pS6K1 protein （390.15± 69.62 vs 50. 59±16.65 ,P〈0. 01）expression in HF group as compared with NC group. Conclusions mTOR/S6K1 signaling pathway plays an important role in the development of higt fat diet induced insulin resistance.

关 键 词：胰岛素抵抗 MTOR 效应因子 

分 类 号：R587[医药卫生—内分泌]