Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas - UNICAMP, Campinas, SP, Brazil.
Mech Ageing Dev. 2010 May;131(5):323-9. doi: 10.1016/j.mad.2010.03.004. Epub 2010 Mar 20.
The insulin resistance associated with aging is improved by exercise, but the molecular mechanisms of this improvement are not fully understood. We investigated whether the improvement in insulin action, associated with acute exercise in old rats is dependent on the modulation of pIRS-1Ser307, JNK, IkBalpha and PTP-1B. Aging rats were subjected to swimming for two 1.5-h long bouts, separated by a 45min rest period. Sixteen hours after the exercise, the rats were killed and proteins from the insulin signaling pathway were analyzed by immunoblotting. Our results show that the reduction in glucose disappearance rate (Kitt), observed in aged rats, was restored at 16h after exercise. Aging led to an increase in Ser307 phosphorylation of IRS-1, and this was reversed by exercise in the skeletal muscle, in parallel with a reduction in pJNK and IkBalpha degradation. Moreover, aging induced an increase in the expression of PTP-1B and attenuated insulin signaling in the muscle of rats, a phenomenon that was reversed by exercise. Interestingly, the decrease in PTP-1B expression in the muscle of exercised old rats was accompanied by an increase in SIRT1 expression. These results provide new insights into the mechanisms by which exercise restores insulin sensitivity during aging.
与衰老相关的胰岛素抵抗可以通过运动得到改善,但这种改善的分子机制尚不完全清楚。我们研究了急性运动是否改善老年大鼠的胰岛素作用,这是否依赖于 pIRS-1Ser307、JNK、IkBalpha 和 PTP-1B 的调节。衰老大鼠进行了两次 1.5 小时的游泳,中间休息 45 分钟。运动后 16 小时,处死大鼠并通过免疫印迹分析胰岛素信号通路中的蛋白质。我们的结果表明,衰老大鼠中观察到的葡萄糖清除率(Kitt)降低在运动后 16 小时得到恢复。衰老导致 IRS-1 的 Ser307 磷酸化增加,而运动则在骨骼肌中逆转了这种情况,同时 pJNK 和 IkBalpha 的降解减少。此外,衰老诱导 PTP-1B 的表达增加,并削弱了大鼠肌肉中的胰岛素信号,这种现象通过运动得到逆转。有趣的是,运动后老年大鼠肌肉中 PTP-1B 表达的降低伴随着 SIRT1 表达的增加。这些结果为运动在衰老过程中恢复胰岛素敏感性的机制提供了新的见解。