Effect of resistance exercise under conditions of reduced blood insulin on AMPKα Ser485/491 inhibitory phosphorylation and AMPK pathway activation
Effect of resistance exercise under conditions of reduced blood insulin on AMPKα Ser485/491 inhibitory phosphorylation and AMPK pathway activation
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DOI：
10.1152/ajpregu.00063.2017
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发表时间：
2017-08-01
影响因子：
2.8
通讯作者：
Fujita, Satoshi
中科院分区：
文献类型：
--
作者：
Kido, Kohei;Yokokawa, Takumi;Fujita, Satoshi
胰岛素通过激活蛋白激酶B/Akt （Akt）通路刺激骨骼肌葡萄糖摄取。最近的研究表明，胰岛素通过磷酸化AMPK α亚基Ser485/491下调AMPK活性。因此，较低的血胰岛素浓度可诱导AMPK信号激活。急性运动是刺激AMPK激活的一种方法；然而，没有研究检查血液胰岛素水平与急性抵抗运动诱导的AMPK通路激活之间的关系。基于先前的研究结果，我们假设急性抵抗运动诱导的AMPK通路激活将通过AMPK α Ser485/491抑制磷酸化的减少而通过胰岛素分泌的中断而增强。为了验证这一假设，10周龄雄性Sprague-Dawley大鼠被注射毒素链脲佐菌素（STZ; 55 mg/kg）破坏分泌胰岛素的β细胞。注射后3 d，采用经皮电刺激法对STZ和对照组大鼠右腓肠肌进行阻力运动。动物在0、1或3小时后被杀死；通过Western blotting和real-time PCR分析肌肉组织中Akt/AMPK及其下游通路的激活情况。值得注意的是，STZ大鼠的基础Akt和AMPK α Ser485/491磷酸化水平显著降低，但运动诱导的AMPK α Thr172和乙酰辅酶a羧化酶（ACC） Ser79磷酸化水平均显著升高。虽然没有发现对抵抗运动诱导的Akt通路激活或葡萄糖摄取有显著影响，但STZ处理可增强抵抗运动诱导的过氧化物酶体增殖体激活受体(PPAR)- γ共激活因子-1 α (PGC-1 α)基因表达。总的来说，这些数据表明，循环胰岛素水平可能调节急性抵抗运动诱导的AMPK通路激活和AMPK依赖性基因表达，这些基因与AMPK α Ser485/491基础磷酸化有关。
Insulin stimulates skeletal muscle glucose uptake via activation of the protein kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP-activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the AMPK alpha-subunit. Thus lower blood insulin concentrations may induce AMPK signal activation. Acute exercise is one method to stimulate AMPK activation; however, no study has examined the relationship between blood insulin levels and acute resistance exercise-induced AMPK pathway activation. Based on previous findings, we hypothesized that the acute resistance exercise-induced AMPK pathway activation would be augmented by disruptions in insulin secretion through a decrease in AMPK alpha Ser485/491 inhibitory phosphorylation. To test the hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting beta-cells. Three days postinjection, the right gastrocnemius muscle from STZ and control rats was subjected to resistance exercise by percutaneous electrical stimulation. Animals were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream pathways in the muscle tissue was analyzed by Western blotting and real-time PCR. Notably, STZ rats showed a significant decrease in basal Akt and AMPK alpha Ser485/491 phosphorylation, but substantial exercise-induced increases in both AMPK alpha Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were observed. Although no significant impact on resistance exercise-induced Akt pathway activation or glucose uptake was found, resistance exercise-induced peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 alpha (PGC-1 alpha) gene expression was augmented by STZ treatment. Collectively, these data suggest that circulating insulin levels may regulate acute resistance exercise-induced AMPK pathway activation and AMPK-dependent gene expression relating to basal AMPK alpha Ser485/491 phosphorylation.