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

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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.