Sharma Naveen, Wang Haiyan, Arias Edward B, Castorena Carlos M, Cartee Gregory D
Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan; School of Health Sciences, Central Michigan University, Mount Pleasant, Michigan;
Muscle Biology Laboratory, School of Kinesiology, University of Michigan, Ann Arbor, Michigan; College of Physical Education and Health, East China Normal University, Shanghai, China;
Am J Physiol Endocrinol Metab. 2015 Apr 1;308(7):E603-12. doi: 10.1152/ajpendo.00618.2014. Epub 2015 Feb 10.
Either calorie restriction [CR; consuming 60-65% of ad libitum (AL) intake] or acute exercise can independently improve insulin sensitivity in old age, but their combined effects on muscle insulin signaling and glucose uptake have previously been unknown. Accordingly, we assessed the independent and combined effects of CR (beginning at 14 wk old) and acute exercise (3-4 h postexercise) on insulin signaling and glucose uptake in insulin-stimulated epitrochlearis muscles from 30-mo-old rats. Either CR alone or exercise alone vs. AL sedentary controls induced greater insulin-stimulated glucose uptake. Combined CR and exercise vs. either treatment alone caused an additional increase in insulin-stimulated glucose uptake. Either CR or exercise alone vs. AL sedentary controls increased Akt Ser(473) and Akt Thr(308) phosphorylation. Combined CR and exercise further elevated Akt phosphorylation on both sites. CR alone, but not exercise alone, vs. AL sedentary controls significantly increased Akt substrate of 160 kDa (AS160) Ser(588) and Thr(642) phosphorylation. Combined CR and exercise did not further enhance AS160 phosphorylation. Exercise alone, but not CR alone, modestly increased GLUT4 abundance. Combined CR and exercise did not further elevate GLUT4 content. These results suggest that CR or acute exercise independently increases insulin-stimulated glucose uptake via overlapping (greater Akt phosphorylation) and distinct (greater AS160 phosphorylation for CR, greater GLUT4 for exercise) mechanisms. Our working hypothesis is that greater insulin-stimulated glucose uptake in the combined CR and exercise group vs. CR or exercise alone relies on greater Akt activation, leading to greater phosphorylation of one or more Akt substrates other than AS160.
热量限制[CR；摄入自由摄食量（AL）的60 - 65%]或急性运动都能独立改善老年个体的胰岛素敏感性，但它们对肌肉胰岛素信号传导和葡萄糖摄取的联合作用此前尚不清楚。因此，我们评估了CR（从14周龄开始）和急性运动（运动后3 - 4小时）对30月龄大鼠胰岛素刺激的肱三头肌中胰岛素信号传导和葡萄糖摄取的独立及联合作用。与AL久坐对照组相比，单独进行CR或单独进行运动均可诱导更高的胰岛素刺激的葡萄糖摄取。CR与运动联合组相比单独进行任何一种处理，均可使胰岛素刺激的葡萄糖摄取进一步增加。与AL久坐对照组相比，单独进行CR或单独进行运动均可增加Akt Ser(473)和Akt Thr(308)的磷酸化。CR与运动联合可进一步提高两个位点的Akt磷酸化水平。与AL久坐对照组相比，单独进行CR而非单独进行运动可显著增加160 kDa的Akt底物（AS160）Ser(588)和Thr(642)的磷酸化。CR与运动联合并未进一步增强AS160的磷酸化。单独进行运动而非单独进行CR可适度增加GLUT4丰度。CR与运动联合并未进一步提高GLUT4含量。这些结果表明，CR或急性运动通过重叠（更大的Akt磷酸化）和不同（CR导致更大的AS160磷酸化，运动导致更大的GLUT4增加）机制独立增加胰岛素刺激的葡萄糖摄取。我们的工作假设是，与单独进行CR或运动相比，CR与运动联合组中更高的胰岛素刺激的葡萄糖摄取依赖于更大的Akt激活，导致除AS160之外的一种或多种Akt底物发生更大程度的磷酸化。
