Universidade Cruzeiro do Sul, Unicsul, São Paulo, SP, Brazil.
Acta Physiol (Oxf). 2010 Jan;198(1):61-9. doi: 10.1111/j.1748-1716.2009.02031.x. Epub 2009 Aug 12.
TRB3 became of major interest in diabetes research when it was shown to interact with and inhibit the activity of Akt. Conversely, physical exercise has been linked to improved glucose homeostasis. Thus, the current study was designed to investigate the effects of acute exercise on TRB3 expression and whole body insulin sensitivity in obese diabetic mice.
Male leptin-deficient (ob/ob) mice swam for two 3-h-long bouts, separated by a 45-min rest period. After the second bout of exercise, food was withdrawn 6 h before antibody analysis. Eight hours after the exercise protocol, the mice were submitted to an insulin tolerance test (ITT). Gastrocnemius muscle samples were evaluated for insulin receptor (IR) and IRS-1 tyrosine phosphorylation, Akt serine phosphorylation, TRB3/Akt association and membrane GLUT4 expression.
Western blot analysis showed that TRB3 expression was reduced in the gastrocnemius of leptin-deficient (ob/ob) mice submitted to exercise when compared with respective ob/ob mice at rest. In parallel, there was an increase in the insulin-signalling pathway in skeletal muscle from leptin-deficient mice after exercise. Furthermore, the GLUT4 membrane expression was increased in the muscle after the exercise protocol. Finally, a single session of exercise improved the glucose disappearance (K(ITT)) rate in ob/ob mice.
Our results demonstrate that acute exercise reverses TRB3 expression and insulin signalling restoration in muscle. Thus, these results provide new insights into the mechanism by which physical activity ameliorates whole body insulin sensitivity in type 2 diabetes.
当 TRB3 被证明与 Akt 相互作用并抑制其活性时，它成为糖尿病研究的主要关注点。相反，体育锻炼与改善葡萄糖稳态有关。因此，本研究旨在研究急性运动对肥胖糖尿病小鼠 TRB3 表达和全身胰岛素敏感性的影响。
雄性瘦素缺乏（ob/ob）小鼠游泳两次，每次 3 小时，中间休息 45 分钟。第二次运动后，撤去食物 6 小时前进行抗体分析。运动方案 8 小时后，对小鼠进行胰岛素耐量试验（ITT）。评估比目鱼肌中胰岛素受体（IR）和 IRS-1 酪氨酸磷酸化、Akt 丝氨酸磷酸化、TRB3/Akt 结合和膜 GLUT4 表达。
Western blot 分析显示，与休息时的 ob/ob 小鼠相比，接受运动的瘦素缺乏（ob/ob）小鼠的比目鱼肌 TRB3 表达减少。平行地，运动后瘦素缺乏小鼠骨骼肌中的胰岛素信号通路增加。此外，运动方案后肌肉中的 GLUT4 膜表达增加。最后，单次运动提高了 ob/ob 小鼠的葡萄糖清除率（K（ITT））。
我们的结果表明，急性运动可逆转肌肉中 TRB3 表达和胰岛素信号的恢复。因此，这些结果为运动改善 2 型糖尿病患者全身胰岛素敏感性的机制提供了新的见解。
