Castorena Carlos M, Arias Edward B, Sharma Naveen, Cartee Gregory D
Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, MI 48109-2214, USA.
Appl Physiol Nutr Metab. 2015 Mar;40(3):251-62. doi: 10.1139/apnm-2014-0412. Epub 2014 Nov 17.
One exercise session can improve subsequent insulin-stimulated glucose uptake by skeletal muscle in healthy and insulin-resistant individuals. Our first aim was to determine whether a brief (2 weeks) high-fat diet (HFD) that caused muscle insulin resistance would activate the mammalian target of rapamycin complex 1 (mTORC1) and/or inhibitor of κB kinase/nuclear factor κB (IKK/NF-κB) pathways, which are potentially linked to induction of insulin resistance. Our second aim was to determine whether acute exercise that improved insulin-stimulated glucose uptake by muscles would attenuate activation of these pathways. We compared HFD-fed rats with rats fed a low-fat diet (LFD). Some animals from each diet group were sedentary and others were studied 3 h postexercise, when insulin-stimulated glucose uptake was increased. The results did not provide evidence that brief HFD activated either the mTORC1 (including phosphorylation of mTOR(Ser2448), TSC2(Ser939), p70S6K(Thr412), and RPS6(Ser235/236)) or the IKK/NF-κB (including abundance of IκBα or phosphorylation of NF-κB(Ser536), IKKα/β(Ser177/181), and IκB(Ser32)) pathway in insulin-resistant muscles. Exercise did not oppose the activation of either pathway, as evidenced by no attenuation of phosphorylation of key proteins in the IKK/NF-κB pathway (NF-κB(Ser536), IKKα/β(Ser177/181), and IκB(Ser32)), unaltered IκBα abundance, and no attenuation of phosphorylation of key proteins in the mTORC1 pathway (mTOR(Ser2448), TSC2(Ser939), and RPS6(Ser235/236)). Instead, exercise induced greater phosphorylation of 2 proteins of the mTORC1 pathway (PRAS40(Thr246) and p70S6K(Thr412)) in insulin-stimulated muscles, regardless of diet. Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF-κB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle.
一次锻炼就能改善健康个体和胰岛素抵抗个体骨骼肌随后的胰岛素刺激的葡萄糖摄取。我们的首要目标是确定导致肌肉胰岛素抵抗的短期（2周）高脂饮食（HFD）是否会激活雷帕霉素复合物1（mTORC1）的哺乳动物靶点和/或κB激酶/核因子κB（IKK/NF-κB）通路，这些通路可能与胰岛素抵抗的诱导有关。我们的第二个目标是确定改善肌肉胰岛素刺激的葡萄糖摄取的急性运动是否会减弱这些通路的激活。我们将高脂饮食喂养的大鼠与低脂饮食（LFD）喂养的大鼠进行了比较。每个饮食组的一些动物 sedentary ，其他动物在运动后3小时进行研究，此时胰岛素刺激的葡萄糖摄取增加。结果没有提供证据表明短期高脂饮食会激活胰岛素抵抗肌肉中的mTORC1（包括mTOR（Ser2448）、TSC2（Ser939）、p70S6K（Thr412）和RPS6（Ser235/236）的磷酸化）或IKK/NF-κB（包括IκBα的丰度或NF-κB（Ser536）、IKKα/β（Ser177/181）和IκB（Ser32）的磷酸化）通路。运动并没有对抗这两种通路的激活，IKK/NF-κB通路中关键蛋白（NF-κB（Ser536）、IKKα/β（Ser177/181）和IκB（Ser32））的磷酸化没有减弱、IκBα丰度未改变以及mTORC1通路中关键蛋白（mTOR（Ser2448）、TSC2（Ser939）和RPS6（Ser235/236））的磷酸化没有减弱都证明了这一点。相反，无论饮食如何，运动都会在胰岛素刺激的肌肉中诱导mTORC1通路的两种蛋白（PRAS40（Thr246）和p70S6K（Thr412））发生更大程度的磷酸化。短期高脂饮食诱导的胰岛素抵抗并非归因于肌肉中mTORC1或IKK/NF-κB通路的更大激活，运动诱导的胰岛素敏感性改善也并非归因于肌肉中这些通路的激活减弱。
