mTOR复合物在有氧运动改善胰岛素抵抗过程中的作用研究

发布时间：2018-03-22 11:12

本文选题：胰岛素抵抗　切入点：有氧运动　出处：《中国运动医学杂志》2015年11期 　论文类型：期刊论文

【摘要】：目的:通过研究8周有氧运动对高脂饮食诱导胰岛素抵抗C57BL/6小鼠肝脏m TOR复合物1/2(m TOR Complex 1/2)以及胰岛素信号相关蛋白的影响,分析有氧运动/高脂饮食与m TORC1/C2和胰岛素信号通路蛋白磷酸化活性之间的关系,为全面理解有氧运动改善高脂饮食诱导机体胰岛素抵抗的机制提供理论依据。方法:选取50只4周龄、雄性C57BL/6小鼠随机分为正常饮食组(C组,n=10)和高脂饮食组(H组,n=40)。高脂饮食组小鼠饲以高脂饮食6周以建立胰岛素抵抗模型,6周后通过口服葡萄糖耐量实验(Oral Glucose Tolerance Test,OGTT)鉴定胰岛素抵抗成模小鼠。随后将胰岛素抵抗小鼠再次随机分为安静组(H组,n=10)和运动组(HE组,n=15),此两组小鼠继续饲以高脂饮食,同时对HE组施以8周、强度为75%VO2max的有氧跑台运动干预。实验结束后,采用OGTT检测小鼠葡萄糖耐量,ELISA法测定空腹血清胰岛素水平,Western Blot检测肝脏Akt/m TOR信号通路相关蛋白磷酸化水平,并通过免疫共沉淀方法检测小鼠肝脏Raptor-m TOR及Rictor-m TOR结合水平。结果:与C组相比,H组小鼠体重、血清胰岛素水平均显著升高,口服葡萄糖耐量下降,肝脏胰岛素信号通路相关蛋白p Akt S473、p Akt T308、p IRS1S307、p AMPKαT172磷酸化水平下降,p S6K1T389磷酸化水平升高。免疫共沉淀检测发现Raptor-m TOR结合水平上升,Rictor-m TOR结合水平下降,即m TORC1蛋白表达水平升高,m TORC2蛋白表达水平减低;与H组相比,HE组小鼠体重、血清胰岛素水平均显著降低,口服葡萄糖耐量增高,肝脏胰岛素信号通路相关蛋白p AktS473、p AktT308、p IRS1S307、p AMPKαT172磷酸化水平有所提高,p S6K1T389磷酸化水平降低。Raptor-m TOR结合减少,Rictor-m TOR结合增多,即m TORC1蛋白表达水平降低,m TORC2蛋白表达水平增高。结论:8周有氧运动可改善高脂饮食诱导小鼠胰岛素敏感性,其机制可能与有氧运动激活小鼠肝脏Akt/m TORC2信号通路、抑制Akt/m TORC1信号通路,增强小鼠肝细胞胰岛素信号敏感性、改善胰岛素抵抗有关。
[Abstract]:Aim: to study the effects of aerobic exercise for 8 weeks on liver m TOR complex 1 / 2 TOR Complex 1 / 2 and insulin signal-related protein in insulin resistant C57BL/6 mice induced by high fat diet. To analyze the relationship between aerobic exercise / high-fat diet and the phosphorylation activity of m TORC1/C2 and insulin signaling pathway protein. To provide a theoretical basis for the comprehensive understanding of the mechanism of aerobic exercise in improving insulin resistance induced by high fat diet. Male C57BL/6 mice were randomly divided into normal diet group (group C) and high-fat diet group (group H). Mice in high-fat diet group were fed high-fat diet for 6 weeks to establish insulin resistance model. The mice with insulin resistance were then randomly divided into two groups: the rest group (H group) and the exercise group (group HE group). The mice of the two groups continued to be fed on a high-fat diet. At the same time, he group was treated with aerobic treadmill exercise with 75%VO2max intensity for 8 weeks. At the end of the experiment, fasting serum insulin level was measured by OGTT, fasting serum insulin level was measured by Elisa and liver Akt/m TOR signal pathway related protein phosphorylation was detected by OGTT. The binding levels of Raptor-m TOR and Rictor-m TOR in liver of mice were detected by immunoprecipitation method. Results: compared with group C, the body weight and serum insulin level in group H were significantly higher than those in group C, and oral glucose tolerance was decreased. Liver insulin signaling pathway associated protein p Akt S473P Akt T308p IRS1S307 AMPK 伪 T172 phosphorylation level decreased and Raptor-m TOR binding level increased and Rictor-m TOR binding level decreased by immunoprecipitation assay. The expression level of m TORC1 protein increased and the expression level of m TORC2 protein decreased, compared with that of H group, the body weight and serum insulin level of mice in HE group decreased significantly, and the oral glucose tolerance increased. The phosphorylation level of hepatic insulin signaling pathway related protein p AktS473pAktT308p IRS307p AMPK 伪 T172 was increased, and the phosphorylation level of S6K1T389 decreased. Raptor-m TOR binding decreased Rictor-m TOR binding. Conclusion aerobic exercise for 8 weeks can improve insulin sensitivity of mice induced by high fat diet, and its mechanism may be related to the activation of Akt/m TORC2 signaling pathway in liver of mice by aerobic exercise. Inhibition of Akt/m TORC1 signaling pathway, enhancement of insulin signal sensitivity and improvement of insulin resistance in hepatocytes of mice.
【作者单位】：天津医科大学基础医学院生理学与病理生理学系;
【基金】：国家自然科学基金(31571220)
【分类号】：R587.1

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