Wojtaszewski J F, Nielsen P, Kiens B, Richter E A
Copenhagen Muscle Research Centre, Department of Human Physiology, University of Copenhagen, Denmark.
Diabetes. 2001 Feb;50(2):265-9. doi: 10.2337/diabetes.50.2.265.
Studies of skeletal muscle from rodents performed both in vivo and in vitro suggest a regulatory role of glycogen synthase kinase (GSK) 3 in glycogen synthase (GS) activation in response to insulin. Recently, hyperinsulinemic clamp studies in humans support such a role under nearly physiological conditions. In addition, in rats the activation of GS in skeletal muscle during treadmill running is time-related to the deactivation of GSK3. We investigated whether GSK3 was deactivated in human muscle during low- (approximately 50% VO2max for 1.5 h) and high-intensity (approximately 75% VO2max for 1 h) bicycle exercise as well as food intake. We observed a small but significant increase in GSK3alpha (10-20%) activity in biopsies obtained from vastus lateralis after both low- and high-intensity exercise, whereas GSK3beta activity was unaffected. Subsequent food intake increased Aktphosphorylation (approximately 2-fold) and deactivated GSK3alpha (approximately 40%), whereas GSK3beta activity was unchanged. GS activity increased in response to both exercise and food intake. We conclude that GSK3alpha but not GSK3beta may have a role in the regulation of GS activity in response to meal-associated hyperinsulinemia in humans. However, in contrast to findings in muscle from rats, exercise does not deactivate GSK3 in humans, suggesting a GSK3-independent mechanism in the regulation of GS activity in muscle during physical activity.
对啮齿动物骨骼肌进行的体内和体外研究表明，糖原合酶激酶（GSK）3在胰岛素刺激下糖原合酶（GS）的激活中起调节作用。最近，对人类进行的高胰岛素钳夹研究支持了在接近生理条件下的这一作用。此外，在大鼠中，跑步机跑步期间骨骼肌中GS的激活与GSK3的失活存在时间关联。我们研究了在低强度（约50%最大摄氧量，持续1.5小时）和高强度（约75%最大摄氧量，持续1小时）自行车运动以及进食过程中，人类肌肉中的GSK3是否失活。我们观察到，在低强度和高强度运动后，从股外侧肌获取的活检样本中，GSK3α活性有小幅但显著的增加（10 - 20%），而GSK3β活性未受影响。随后的进食增加了Akt磷酸化（约2倍）并使GSK3α失活（约40%），而GSK3β活性保持不变。运动和进食均使GS活性增加。我们得出结论，在人类中，GSK3α而非GSK3β可能在与进餐相关的高胰岛素血症反应中对GS活性的调节起作用。然而，与大鼠肌肉中的研究结果相反，运动并不会使人类肌肉中的GSK3失活，这表明在体力活动期间，肌肉中GS活性的调节存在一种不依赖GSK3的机制。
