Role of AMP kinase and calcineurin for skeletal muscle histochemical and biochemical adaptations : skeletal muscle signal transduction by endurance training

AMPK被认为是骨骼肌耐力训练的信号转导因子之一。大鼠在跑台上跑步，立即切除比目鱼肌，测定AMPK的磷酸化。然后，作为AMPK特异性激活剂AICAR，AMPK的磷酸化显著增加。训练14d后，大鼠比目鱼肌转录辅活化子PGC-1α、转录因子PPARδ和葡萄糖转运蛋白4蛋白表达增加，CS、MDH和β等氧化酶活性增加。这些结果表明，耐力训练对骨骼肌代谢的适应至少部分与AMPK有关。此外，AMPK的激活可能会增加PGC-1α和PPARδ的表达，从而增强氧化酶的活性。接下来的实验中，给大鼠服用能激活AMPK的抗糖尿病药物二甲双胍，为期14天。然后，骨骼肌PGC-1α蛋白表达显著增加。此外，二甲双胍还能提高包括CS和β在内的氧化酶活性。这些结果提出了二甲双胍至少部分改善糖尿病病情的可能性，其机制与耐力运动训练相同。我们还研究了钙调神经磷酸酶的作用，它被认为是骨骼肌耐力训练的另一个信号转导因素。用钙调神经磷酸酶抑制剂处理后，骨骼肌糖酵解酶活性增加，而氧化酶活性没有变化。提示钙调神经磷酸酶在耐力运动训练降低糖酵解酶活性中起一定作用。

AMP kinase (AMPK) was considered as one of the signal transduction factors with endurance training in skeletal muscle. The rats ran on treadmill and immediately soleus muscle was excised for determining AMPK phosphorylation. Then, AMPK phosphorylation was significantly increased as AMPK specific activator AICAR. The rats were trained such exercise for 14 days and then soleus muscle transcriptional coactivator PGC-1α, transcriptional factor PPARδ, and glucose transporter 4 protein expressions and oxidative enzyme activities such as CS, MDH, and βHAD were increased. These results would suggest that metabolic adaptations of skeletal muscle by endurance training are at least in part related to AMPK. In addition, AMPK activation might increase PGC-1α and PPARδ expression that enhances the oxidative enzyme activities. In the next, anti-diabetic drug metformin, which can activate AMPK, was administered to the rats for 14 days. Then, skeletal muscle PGC-1α protein expression was significantly increased. Furthermore, oxidative enzyme activities including CS and βHAD were increased by metformin treatment as AICAR. These results raise the possibility that metformin at least partially improves the diabetic conditions as the same mechanisms of the endurance exercise training. We also examine the role of calcineurin which is considered another signal transduction factors with endurance training in skeletal muscle. The rats were treated with calcineurin inhibitor and then skeletal muscle glycolytic enzyme activities were increased without any change of oxidative enzyme activities. The results may imply that calcineurin play a role for the decrease of glycolytic enzyme activities by endurance exercise training.