mTOR/S6K1信号通路与有氧运动改善小鼠高脂饮食诱导胰岛素抵抗间的关系  

A study on the relationship of mTOR/S6K1 signaling pathway and aerobic exercises attenuating insulin resistance induced by high fat diet in mice

作　　者：苑红[1] 牛燕媚[1] 刘彥辉 苏照鹏[1] 李慧阁[1] 姜宁[1] 傅力[1] 

机构地区：[1]天津体育学院运动人体科学系,300381

出　　处：《中国康复医学杂志》2009年第4期297-302,I0001,共7页Chinese Journal of Rehabilitation Medicine

基　　金：国家自然科学基金(30570898和30871213);天津市重大攻关(05YFGDSF02100)

摘　　要：目的:探讨有氧运动对胰岛素抵抗小鼠骨骼肌中mTOR/S6K1和PGC-1α的影响,分析其分子生物学机制。方法:C57BL/6小鼠高脂饮食喂养8周以建立胰岛素抵抗模型。后小鼠随机分为安静组(HC)和运动组(HE)。HE组施以6周跑台有氧训练。实验结束后采用OGTT检测葡萄糖耐量,组织学检测胰岛形态变化。ELISA法检测血清空腹胰岛素水平,Northern blot、Western blot和免疫荧光法检测骨骼肌中mTOR、S6K1及其磷酸化蛋白(pS6K1-Thr389)和PGC-1α mRNA和蛋白的表达。结果:与HC组相比,小鼠HE组6周有氧运动后体重、空腹血清胰岛素值和胰岛β细胞团面积百分比均呈显著下降;葡萄糖耐量也得到明显改善;骨骼肌中mTOR、S6K1、pS6K1-Thr389 mRNA和蛋白表达均明显降低,而PGC-1α mRNA和蛋白明显升高。结论:有氧运动明显增加了机体组织对胰岛素的敏感性,推测有氧运动可能通过抑制mTOR/S6K1信号通路,增加胰岛素抵抗小鼠骨骼肌的能量代谢从而改善胰岛素抵抗。Objective： To investigate the effects of aerobic exercise on mTOR/S6K1 and PGC-1α in mice with insulin resistance, and it＇s possible mechanisms. Method： C57BL/6 male mice fed with high fat diet for 8 weeks were proved to establish insulin resistance models. Afterward mice were randomly divided to HC （high fat diet, no exercise） and HE （high fat diet＋exercise） groups. Mice in HE group were submitted to treadmill aerobic training for 6 weeks. By the end of training, the changes of glucose tolerance by oral glucose tolerance test （OGTF） and morphology of pancreatic islets under microscope were observed. Insulin concentration was measured by ELISA. Northern blot, Western blot and immunofluoreseence examination. All tests were performed to detect mTOR,S6K1 （and/or pS6K1-Thr^389 and PGC-1α mRNA and protein expression in skeletal muscle. Result： By comparing with HC group, after 6 week aerobic exercises the body weight, fasting serum insulin level and area of pancreatic islets of mice in HE group decreased significantly. Furthermore, OGTT improved. The expressions of roTOR, S6K1 （and/or pS6K1-Th^389） mRNA and protein decreased significantly. PGC-1α mRNA and protein level increased markedly in skeletal muscles in HE group. Conclusion： Aerobic exercises attenuates insulin resistance by inhibiting activity of mTOR/S6K1 signaling pathway, activating energy metabolism and then elevating skeletal muscle insulin sensitivity.

关 键 词：胰岛素抵抗 有氧运动 哺乳动物 雷帕霉素靶蛋白 核糖体S6激酶1 过氧化物酶体增殖物激活受体Γ 辅激活因子α 

分 类 号：R587.1[医药卫生—内分泌] R493[医药卫生—内科学]