Effects of Exercise-Induced Activation of 5'AMP-Activated Protein Kinase (AMPK) on Glucose Metabolism in Skeletal Muscle

运动是骨骼肌葡萄糖代谢的有效刺激物。AMPK是由催化α和调节β和γ亚基组成的异源三聚体蛋白，并且在骨骼肌中响应于运动而被快速激活。本研究的主要目的是确定收缩刺激AMPK是否在调节肌肉葡萄糖代谢中起作用。哺乳动物骨骼肌表达两种不同的α亚型：α1和α2。超生理性收缩，如电刺激引起的强直性收缩，激活了α1和α2，但中等强度的运动，如跑步机跑步，选择性地激活了大鼠骨骼肌中的α2。α2活性以运动强度和持续时间依赖性方式增加，与胰岛素非依赖性葡萄糖转运活性平行。此外，药理学抑制α2显著抑制体外大鼠肌肉中收缩刺激的葡萄糖转运。与动物肌肉的观察结果类似， ...更多信息 在人骨骼肌中，已证实能激活葡萄糖转运的耐力运动（= 70%VO2max）刺激α2，但不刺激α1。通过腹膜内或皮下注射AICAR的药理学α-2激活激活小鼠骨骼肌中的葡萄糖转运，达到与中等强度运动响应相似的程度。此外，与长期运动训练的效果类似，反复注射AICAR 4-7天显著增加小鼠骨骼肌中的葡萄糖转运蛋白GLUT 4。这些结果表明，AMPKα2是导致运动刺激的葡萄糖转运和GLUT 4表达的信号中介，而AMPK似乎在运动刺激的骨骼肌糖原代谢中不起主要作用。当大鼠肌肉在噻唑烷二酮类（广泛使用的抗糖尿病药物）存在下孵育时，α2与胰岛素非依赖性葡萄糖转运活性平行显著刺激。除了增加胰岛素敏感性的常规作用外，噻唑烷二酮类药物可能通过AMPK依赖性机制对骨骼肌葡萄糖转运具有运动样作用。少

Exercise is a potent stimulator of glucose metabolism in skeletal muscle. AMPK is a heterotrimeric protein consisting of catalytic α and regulatory β and γ subunits, and is rapidly activated in response to exercise in skeletal muscle. The main purpose of the present study was to determine if contraction-stimulated AMPK plays a role in regulating muscle glucose metabolism. Mammalian skeletal muscle expresses two distinct α isoforms: α1 and α2. Supraphysiological contraction, such as tetanic contraction by electromyostimulation, activated both α1 and α2, but moderate-intensity exercise such as treadmill running selectively activated α2 in rat skeletal muscle. α2 activity was increased in an exercise intensity- and duration-dependent manner, in parallel with insulin-independent glucose transport activity. Furthermore, pharmacological inhibition of α2 significantly inhibited contraction-stimulated glucose transport in rat muscles in vitro. Similar to the observations of animal muscles, end … More urance exercise (= 70 %VO2max) that had been shown to activate glucose transport stimulated α2, but not α1 in human skeletal muscle. Pharmacological α-2 activation by intraperitoneal or subcutaneous injection of AICAR activated glucose transport in mouse skeletal muscle, to a similar extent that was achieved in response to moderate-intensity exercise. In addition, similar to the effect of chronic exercise training, repeated injections of AICAR for 4-7 days significantly increased glucose transporter GLUT4 in mouse skeletal muscle. These results suggest that AMPKα2 is a signaling intermediary leading to exercise-stimulated glucose transport and GLUT4 expression, while AMPK does not seem to play a major role in exercise-stimulated glycogen metabolism in skeletal muscle. When rat muscles were incubated in the presence of thiazolidinediones, widely prescribed antidiabetic reagents, α2 was significantly stimulated in parallel with insulin-independent glucose transport activity. In addition to the conventional effect of increasing insulin sensitivity, thiazolidinediones may have an exercise-like effect on skeletal muscle glucose transport via AMPK-dependent mechanism. Less