Chibalin A V, Yu M, Ryder J W, Song X M, Galuska D, Krook A, Wallberg-Henriksson H, Zierath J R
Department of Surgical Sciences, Karolinska Hospital, S-171 76, Karolinska Institutet, S-171 77, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2000 Jan 4;97(1):38-43. doi: 10.1073/pnas.97.1.38.
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-1 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-1, 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-1 and IRS-2 to exercise suggests that these molecules have specialized, rather than redundant, roles in insulin signaling in skeletal muscle.
体力活动水平与改善葡萄糖稳态相关。我们确定运动是否会改变骨骼肌中参与胰岛素信号转导的蛋白质的表达和/或活性。Wistar大鼠每天游泳6小时，持续1天或5天。在最后一次运动 bout 后16小时切除肱三头肌，并在有或无胰岛素（120 nM）的情况下孵育。运动1天和5天后，胰岛素刺激的葡萄糖转运分别增加了30%和50%。运动1天和5天后，糖原含量分别增加了2倍和4倍，糖原合酶表达没有变化。葡萄糖转运蛋白GLUT4和胰岛素受体的蛋白质表达在运动1天后增加了2倍，运动5天后没有进一步变化。运动5天后，胰岛素刺激的受体酪氨酸磷酸化增加了2倍。尽管运动5天后IRS-1蛋白含量降低了50%，但运动1天和5天后，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激酶活性分别增加了2.5倍和3.5倍。运动1天后，IRS-2蛋白表达增加了2.6倍，基础和胰岛素刺激的IRS-2相关PI 3激酶活性分别增加了2.8倍和9倍。与IRS-1相反，运动5天后，IRS-2表达和相关的PI 3激酶活性恢复到久坐水平。运动5天后，胰岛素刺激的Akt磷酸化增加了5倍。总之，运动后胰岛素刺激的葡萄糖转运增加不仅限于GLUT4表达的增加。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，这些分子在骨骼肌胰岛素信号传导中具有专门的而非冗余的作用。
