Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: Differential effects on insulin-receptor substrates 1 and 2
Exercise-induced changes in expression and activity of proteins involved in insulin signal transduction in skeletal muscle: Differential effects on insulin-receptor substrates 1 and 2
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DOI：
10.1073/pnas.97.1.38
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发表时间：
2000-01-04
影响因子：
11.1
通讯作者：
Zierath, JR
中科院分区：
文献类型：
--
作者：
Chibalin, AV;Yu, M;Zierath, JR
身体活动水平与改善葡萄糖稳态有关。我们确定了运动是否改变了骨骼肌中胰岛素信号转导相关蛋白的表达和/或活性。Wistar大鼠每天游泳6 h，连续1 ~ 5 d。在最后一次运动后16小时切除滑车上肌，并与或不与胰岛素（120 nM）一起孵育。胰岛素刺激的葡萄糖转运增加30%和50%后，1和5天的运动，分别。糖原含量增加2和4倍后，1和5天的运动，糖原合成酶的表达没有变化。葡萄糖转运蛋白GLUT 4和胰岛素受体的蛋白表达在1天后增加了2倍，在运动5天后没有进一步的变化。运动5天后，胰岛素刺激受体酪氨酸磷酸化增加2倍。胰岛素刺激的胰岛素受体底物（IRS）1的酪氨酸磷酸化和相关的磷脂酰肌醇（PI）3-激酶活性增加2.5-和3.5-倍后，1和5天的运动，尽管减少（50%）IRS-1蛋白含量后，5天的运动。运动1天后，IRS-2蛋白表达增加2.6倍，基础和胰岛素刺激的IRS-2相关PI 3激酶活性分别增加2.8倍和9倍。与IRS-1相反，IRS-2表达和相关的PI 3-激酶活性在运动5天后正常化至久坐水平。胰岛素刺激的Akt磷酸化在运动5天后增加了5倍。总之，运动后胰岛素刺激的葡萄糖转运增加不仅限于GLUT 4表达增加。运动导致参与胰岛素信号转导的几种蛋白质的表达和功能增加。此外，IRS-1和IRS-2对运动的不同反应表明，这些分子在骨骼肌中的胰岛素信号传导中具有专门的而不是多余的作用。
Level of physical activity is linked to improved glucose homeostasis. We determined whether exercise alters the expression and/or activity of proteins involved in insulin-signal transduction in skeletal muscle. Wistar rats swam 6 h per day for 1 or 5 days. Epitrochlearis muscles were excised 16 h after the last exercise bout, and were incubated with or without insulin (120 nM). Insulin-stimulated glucose transport increased 30% and 50% after 1 and 5 days of exercise, respectively. Glycogen content increased 2- and 4-fold after 1 and 5 days of exercise, with no change in glycogen synthase expression. Protein expression of the glucose transporter GLUT4 and the insulin receptor increased 2-fold after 1 day, with no further change after 5 days of exercise. Insulin-stimulated receptor tyrosine phosphorylation increased 2-fold after 5 days of exercise. Insulin-stimulated tyrosine phosphorylation of insulin-receptor substrate (IRS) 1 and associated phosphatidylinositol (PI) 3-kinase activity increased 2.5- and 3.5-fold after 1 and 5 days of exercise, despite reduced (50%) IRS-l protein content after 5 days of exercise. After 1 day of exercise, IRS-2 protein expression increased 2.6-fold and basal and insulin-stimulated IRS-2 associated PI 3-kinase activity increased 2.8-fold and 9-fold, respectively. In contrast to IRS-l, IRS-2 expression and associated PI 3-kinase activity normalized to sedentary levels after 5 days of exercise. Insulin-stimulated Akt phosphorylation increased 5-fold after 5 days of exercise. In conclusion, increased insulin-stimulated glucose transport after exercise is not limited to increased GLUT4 expression. Exercise leads to increased expression and function of several proteins involved in insulin-signal transduction. Furthermore, the differential response of IRS-l and IRS-2 to exercise suggests that these molecules have specialized, rather than redundant, roles in insulin signaling in skeletal muscle.