Department and Institute of Physiology, School of Medicine, National Yang Ming University, Taipei, Republic of China.
High Alt Med Biol. 2011 Winter;12(4):371-8. doi: 10.1089/ham.2010.1088.
The skeletal muscle AMP-activated protein kinase (AMPK)-related glucose transport pathway is involved in glucose homeostasis.
In this study, we examined whether obese control Zucker rats had abnormal expression of proteins in the LKB1-AMPK-AS160-GLUT4 pathway in red gastrocnemius muscle compared to that in lean (normal) control Zucker rats. We also compared the chronic training effects of exercise, hypoxia, and altitude training on this pathway in lean and obese rats.
At sea level, lean and obese rats were divided into 4 groups for 6 weeks training as follows: 1) control; 2) exercise (progressive daily swimming-exercise training with comparable exercise signals between the two groups); 3) hypoxia (8 hours of daily 14% O2 exposure); and 4) exercise plus hypoxia (also called altitude training). Seven animals were used for each group.
The obese rats in the control group had higher body weights, elevated fasting insulin and glucose levels, and higher baseline levels of muscle AMPK and AS160 phosphorylation compared with those of lean control rats. For obese Zucker rats in the exercise or hypoxia groups, the muscle AMPK phosphorylation level was significantly decreased compared with that of the control group. For obese Zucker rats in the altitude training group, the levels of AMPK, AS160 phosphorylation, fasting insulin, and fasting glucose were decreased concomitant with an approximate 50% increase in the muscle GLUT4 protein level compared with those of the control group. In lean rats, the altitude training efficiently lowered fasting glucose and insulin levels and increased muscle AMPK and AS160 phosphorylation as well as GLUT4 protein levels.
Our results provide evidence that long-term altitude training may be a potentially effective nonpharmacological strategy for treating and preventing insulin resistance based on its effects on the skeletal muscle AMPK-AS160-GLUT4 pathway.
骨骼肌 AMP 激活的蛋白激酶（AMPK）相关的葡萄糖转运途径与葡萄糖稳态有关。
本研究旨在探讨肥胖对照 Zucker 大鼠红腓肠肌中 LKB1-AMPK-AS160-GLUT4 通路相关蛋白的表达是否异常，与 lean（正常）对照 Zucker 大鼠相比。我们还比较了运动、低氧和高原训练对 lean 和肥胖大鼠该途径的慢性训练效应。
在海平面，将 lean 和肥胖大鼠分为 4 组，进行 6 周的训练，如下：1）对照组；2）运动（两组运动信号相当的渐进性每日游泳运动训练）；3）低氧（每日 14%O2 暴露 8 小时）；和 4）运动加低氧（也称为高原训练）。每组 7 只动物。
对照组肥胖大鼠体重较高，空腹胰岛素和血糖水平升高，肌肉 AMPK 和 AS160 磷酸化水平基线较高。与对照组相比，运动或低氧组肥胖 Zucker 大鼠的肌肉 AMPK 磷酸化水平显著降低。与对照组相比，高原训练组肥胖 Zucker 大鼠的 AMPK、AS160 磷酸化、空腹胰岛素和空腹血糖水平降低，同时肌肉 GLUT4 蛋白水平约增加 50%。在 lean 大鼠中，高原训练有效地降低了空腹血糖和胰岛素水平，并增加了肌肉 AMPK 和 AS160 磷酸化以及 GLUT4 蛋白水平。
我们的研究结果提供了证据，表明长期高原训练可能是一种有效的非药物治疗策略，可基于其对骨骼肌 AMPK-AS160-GLUT4 途径的影响来治疗和预防胰岛素抵抗。
