Faculty of Sport and Health Science, Ritsumeikan University, Kusatsu, Shiga, Japan.
Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.
Sci Rep. 2020 May 22;10(1):8509. doi: 10.1038/s41598-020-65397-z.
Acute aerobic exercise (AE) increases skeletal muscle insulin sensitivity for several hours, caused by acute activation of AMP-activated protein kinase (AMPK). Acute resistance exercise (RE) also activates AMPK, possibly improving insulin-stimulated glucose uptake. However, RE-induced rapamycin-sensitive mechanistic target of rapamycin complex 1 (mTORC1) activation is higher and has a longer duration than after AE. In molecular studies, mTORC1 was shown to be upstream of insulin receptor substrate 1 (IRS-1) Ser phosphorylation residue, inducing insulin resistance. Therefore, we hypothesised that although RE increases insulin sensitivity through AMPK activation, prolonged mTORC1 activation after RE reduces RE-induced insulin sensitising effect. In this study, we used an electrical stimulation-induced RE model in rats, with rapamycin as an inhibitor of mTORC1 activation. Our results showed that RE increased insulin-stimulated glucose uptake following AMPK signal activation. However, mTORC1 activation and IRS-1 Ser632/635 and Ser612 phosphorylation were elevated 6 h after RE, with concomitant impairment of insulin-stimulated Akt signal activation. By contrast, rapamycin inhibited these prior exercise responses. Furthermore, increases in insulin-stimulated skeletal muscle glucose uptake 6 h after RE were higher in rats with rapamycin treatment than with placebo treatment. Our data suggest that mTORC1/IRS-1 signaling inhibition enhances skeletal muscle insulin-sensitising effect of RE.
急性有氧运动 (AE) 会使骨骼肌对胰岛素的敏感性在数小时内增强，这是由 AMP 激活的蛋白激酶 (AMPK) 的急性激活引起的。急性抗阻运动 (RE) 也会激活 AMPK，可能会改善胰岛素刺激的葡萄糖摄取。然而，RE 诱导的雷帕霉素敏感的雷帕霉素靶蛋白复合物 1(mTORC1)的激活比 AE 更高且持续时间更长。在分子研究中，mTORC1 被证明是胰岛素受体底物 1 (IRS-1) Ser 磷酸化残基的上游，导致胰岛素抵抗。因此，我们假设，尽管 RE 通过 AMPK 激活增加胰岛素敏感性，但 RE 后 mTORC1 的持续激活会降低 RE 诱导的胰岛素增敏作用。在这项研究中，我们使用电刺激诱导的 RE 大鼠模型，用雷帕霉素作为 mTORC1 激活的抑制剂。我们的结果表明，RE 增加了 AMPK 信号激活后的胰岛素刺激的葡萄糖摄取。然而，RE 后 6 小时 mTORC1 激活以及 IRS-1 Ser632/635 和 Ser612 磷酸化增加，同时伴随着胰岛素刺激的 Akt 信号激活受损。相比之下，雷帕霉素抑制了这些先前的运动反应。此外，雷帕霉素处理的大鼠在 RE 后 6 小时胰岛素刺激的骨骼肌葡萄糖摄取增加高于安慰剂处理的大鼠。我们的数据表明，mTORC1/IRS-1 信号抑制增强了 RE 对骨骼肌的胰岛素增敏作用。
