An AMPK/Axin1-Rac1 Signaling Pathway Mediates Contraction-regulated Glucose Uptake in Skeletal Muscle Cells.
An AMPK/Axin1-Rac1 Signaling Pathway Mediates Contraction-regulated Glucose Uptake in Skeletal Muscle Cells.
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DOI：
10.1152/ajpendo.00272.2019
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发表时间：
2019-12
期刊：
影响因子：
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通讯作者：
Yingying Yue;Chang Zhang;Xuejiao Zhang;Shitian Zhang;Qian Liu;Fang Hu;X. Lv;Hanqi Li;
中科院分区：
文献类型：
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作者：
Yingying Yue;Chang Zhang;Xuejiao Zhang;Shitian Zhang;Qian Liu;Fang Hu;X. Lv;Hanqi Li;
收缩主要通过激活AMPK和Rac 1刺激骨骼肌葡萄糖摄取。然而，收缩如何激活这些信号蛋白的分子细节尚不清楚。最近，Axin 1已被证明在葡萄糖饥饿依赖的AMPK激活过程中与AMPK和LKB 1形成复合物。在这里，我们证明了电脉冲刺激（EPS）收缩C2 C12肌管或C57 BL/6小鼠的跑步机运动增强了Axin 1和AMPK从肌管裂解物或腓肠肌组织的相互免疫共沉淀。有趣的是，EPS或运动，上调总细胞Axin 1水平的AMPK依赖的方式在C2 C12肌管和腓肠肌小鼠肌肉，分别。此外，用AICAR处理C2 C12肌管或腓肠肌直接激活AMPK提高了Axin 1蛋白水平。另一方面，siRNA介导的Axin 1敲低减少了收缩肌管中AMPK的激活。此外，用化合物C抑制AMPK或siRNA介导的AMPK或Axin 1敲低阻断了Rac 1的收缩诱导的GTP负载、PAK磷酸化和收缩刺激的葡萄糖摄取。总之，我们的研究结果表明AMPK/Axin 1-Rac 1信号通路介导收缩刺激的骨骼肌葡萄糖摄取。
Contraction stimulates skeletal muscle glucose uptake predominantly through activation of AMPK and Rac1. However, the molecular details of how contraction activates these signaling proteins is not clear. Recently, Axin1 has been shown to form a complex with AMPK and LKB1 during glucose-starvation dependent activation of AMPK. Here, we demonstrate electrical pulse stimulated (EPS) contraction of C2C12 myotubes or treadmill exercise of C57BL/6 mice enhanced reciprocal co-immunoprecipitation of Axin1 and AMPK from myotube lysates or gastrocnemius muscle tissue. Interestingly, EPS or exercise, upregulated total cellular Axin1 levels in an AMPK-dependent manner in C2C12 myotubes and gastrocnemius mouse muscle, respectively. Also, direct activation of AMPK with AICAR treatment of C2C12 myotubes or gastrocnemius muscle elevated Axin1 protein levels. On the other hand, siRNA-mediated Axin1 knockdown lessened activation of AMPK in contracted myotubes. Further, AMPK inhibition with Compound C or siRNA-mediated knockdown of AMPK or Axin1, blocked contraction-induced GTP-loading of Rac1, PAK phosphorylation and contraction-stimulated glucose uptake. In summary, our results suggest that an AMPK/Axin1-Rac1 signaling path way mediates contraction-stimulated skeletal muscle glucose uptake.