Caffeine acutely activates 5′adenosine monophosphate-activated protein kinase and increases insulin-independent glucose transport in rat skeletal muscles
Caffeine acutely activates 5′adenosine monophosphate-activated protein kinase and increases insulin-independent glucose transport in rat skeletal muscles
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DOI：
10.1016/j.metabol.2009.05.013
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发表时间：
2009-11-01
影响因子：
9.8
通讯作者：
Hayashi, Tatsuya
中科院分区：
文献类型：
--
作者：
Egawa, Tatsuro;Hamada, Taku;Hayashi, Tatsuya
咖啡因（1，3，7-三甲基黄嘌呤）与葡萄糖和脂质代谢的调节有关，包括胰岛素非依赖性葡萄糖转运、葡萄糖转运蛋白4表达和骨骼肌中脂肪酸利用等作用。这些作用与运动诱导的和5 '腺苷一磷酸活化蛋白激酶（AMPK）介导的骨骼肌代谢变化相似，表明咖啡因通过AMPK活化参与肌肉代谢的调节。我们探讨了咖啡因是否作用于骨骼肌以刺激AMPK。用含咖啡因的Krebs缓冲液孵育大鼠上滑车肌和比目鱼肌（>= 3 mmol/L，> 15分钟），以剂量和时间依赖性方式增加AMPK α Thr（172）和乙酰辅酶A羧化酶Ser（79）的磷酸化，AMPK α Thr（172）是激酶完全激活的关键步骤，乙酰辅酶A羧化酶Ser（79）是AMPK的下游靶点。同工型特异性AMPK活性分析显示AMPK α 1和α 2活性均显著增加。这种酶的激活与磷酸肌酸含量的减少和3-O-甲基-D-葡萄糖转运活性的增加有关。这些结果表明，咖啡因通过急性刺激骨骼肌AMPK活性和胰岛素非依赖性葡萄糖转运，降低细胞内能量状态，具有与运动相似的作用。(C)2009 Elsevier Inc. All rights reserved.
Caffeine (1,3,7-trimethylxanthine) has been implicated in the regulation of glucose and lipid metabolism including actions Such as insulin-independent glucose transport, glucose transporter 4 expression, and fatty acid utilization in skeletal muscle. These effects are similar to the exercise-induced and 5'adenosine monophosphate-activated protein kinase (AMPK)-mediated metabolic changes in skeletal muscle, suggesting that caffeine is involved in the regulation of muscle metabolism through AMPK activation. We explored whether caffeine acts on skeletal muscle to stimulate AMPK. Incubation of rat epitrochlearis and soleus muscles with Krebs buffer containing caffeine (>= 3 mmol/L, > 15 minutes) increased the phosphorylation of AMPK alpha Thr(172), an essential step for full kinase activation, and acetyl-coenzyme A carboxylase Ser(79), a downstream target of AMPK, in dose- and time-dependent manners. Analysis of isoform-specific AMPK activity revealed that both AMPK alpha 1 and alpha 2 activities increased significantly. This enzyme activation was associated with a reduction in phosphocreatine content and an increased rate of 3-O-methyl-D-glucose transport activity in the absence of insulin, These results suggest that caffeine has similar actions to exercise by acutely Stimulating skeletal Muscle AMPK activity and insulin-independent glucose transport with a reduction of the intracellular energy status. (C) 2009 Elsevier Inc. All rights reserved.