Wright David C, Hucker Kathleen A, Holloszy John O, Han Dong Ho
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Diabetes. 2004 Feb;53(2):330-5. doi: 10.2337/diabetes.53.2.330.
It is now generally accepted that activation of AMP-activated protein kinase (AMPK) is involved in the stimulation of glucose transport by muscle contractions. However, earlier studies provided evidence that increases in cytosolic Ca(2+) mediate the effect of muscle contractions on glucose transport. The purpose of this study was to test the hypothesis that both the increase in cytosolic Ca(2+) and the activation of AMPK are involved in the stimulation of glucose transport by muscle contractions. Caffeine causes release of Ca(2+) from the sarcoplasmic reticulum. Incubation of rat epitrochlearis muscles with a concentration of caffeine that raises cytosolic Ca(2+) to levels too low to cause contraction resulted in an approximate threefold increase in glucose transport. Caffeine treatment also resulted in increased phosphorylation of calmodulin-dependent protein kinase (CAMK)-II in epitrochlearis muscle. The stimulation of glucose transport by caffeine was blocked by the Ca(2+)-CAMK inhibitors KN62 and KN93. Activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) also resulted in an approximate threefold increase in glucose transport in the epitrochlearis. The increases in glucose transport induced by AICAR and caffeine were additive, and their combined effect was not significantly different from that induced by maximally effective contractile activity. KN62 and KN93 caused an approximately 50% inhibition of the stimulation of glucose transport by contractile activity. Our results provide evidence that both Ca(2+) and AMPK are involved in the stimulation of glucose transport by muscle contractions. They also suggest that the stimulation of glucose transport by Ca(2+) involves activation of CAMK.
现在人们普遍认为，AMP激活的蛋白激酶（AMPK）的激活参与了肌肉收缩对葡萄糖转运的刺激作用。然而，早期研究提供的证据表明，胞质Ca(2+)的增加介导了肌肉收缩对葡萄糖转运的影响。本研究的目的是检验以下假设：胞质Ca(2+)的增加和AMPK的激活均参与了肌肉收缩对葡萄糖转运的刺激作用。咖啡因可导致肌浆网释放Ca(2+)。用能将胞质Ca(2+)升高到过低水平而无法引起收缩的咖啡因浓度孵育大鼠肱三头肌，导致葡萄糖转运增加约三倍。咖啡因处理还导致肱三头肌中钙调蛋白依赖性蛋白激酶（CAMK）-II的磷酸化增加。咖啡因对葡萄糖转运的刺激作用被Ca(2+)-CAMK抑制剂KN62和KN93阻断。用5-氨基咪唑-4-甲酰胺核苷（AICAR）激活AMPK也导致肱三头肌中葡萄糖转运增加约三倍。AICAR和咖啡因诱导的葡萄糖转运增加是相加的，它们的联合作用与最大有效收缩活动诱导的作用无显著差异。KN62和KN93对收缩活动刺激葡萄糖转运的作用产生了约50%的抑制。我们的结果提供了证据，表明Ca(2+)和AMPK均参与了肌肉收缩对葡萄糖转运的刺激作用。它们还表明，Ca(2+)对葡萄糖转运的刺激作用涉及CAMK的激活。
