Electrical pulse stimulation induces GLUT4 translocation in a Rac‐Akt‐dependent manner in C2C12 myotubes
Electrical pulse stimulation induces GLUT4 translocation in a Rac‐Akt‐dependent manner in C2C12 myotubes
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DOI：
10.1002/1873-3468.12982
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发表时间：
2018-02
期刊：
影响因子：
3.5
通讯作者：
Fang Hu;Nana Li;Zhu Li;Chang Zhang;Yingying Yue;Qian Liu;Liming Chen;P. Bilan;W. Niu
中科院分区：
文献类型：
--
作者：
Fang Hu;Nana Li;Zhu Li;Chang Zhang;Yingying Yue;Qian Liu;Liming Chen;P. Bilan;W. Niu
肌肉收缩会增加骨骼肌葡萄糖的摄取，但其潜在机制尚未完全阐明。虽然 Akt 对于胰岛素刺激的葡萄糖摄取很重要，但在收缩刺激的肌肉葡萄糖摄取中的作用存在争议。在我们的研究中，C2C12 骨骼肌肌管通过电脉冲刺激 (EPS) 收缩。我们发现 EPS 以时间依赖性方式导致 S473 和 T308 位点上的 Akt 磷酸化。 Akt 抑制剂 MK2206 部分减少 EPS 刺激的 GLUT4 易位，而不影响 EPS 刺激的 AMPK 磷酸化。 EPS 激活 Rac1 GTP 结合，EPS 刺激的 GLUT4 易位被 Rac1 抑制剂 II 和 siRac1 部分抑制。有趣的是，Rac1 抑制剂 II 和 siRac1 均抑制 EPS 刺激的 Akt 在位点 S473 和 T308 上的磷酸化。我们的研究结果表明，C2C12 肌管中 EPS 刺激的 GLUT4 易位涉及 Rac1-Akt 信号通路。
Muscle contraction increases skeletal muscle glucose uptake, but the underlying mechanisms are not fully elucidated. While important for insulin‐stimulated glucose uptake, the role of Akt in contraction‐stimulated muscle glucose uptake is controversial. In our study, C2C12 skeletal muscle myotubes were contracted by electrical pulse stimulation (EPS). We found that EPS leads to Akt phosphorylation on sites S473 and T308 in a time‐dependent manner. The Akt inhibitor MK2206 partly reduces EPS‐stimulated GLUT4 translocation without affecting EPS‐stimulated AMPK phosphorylation. EPS activates Rac1 GTP‐binding, and EPS‐stimulated GLUT4 translocation is partly inhibited by Rac1 inhibitor II and siRac1. Interestingly, both Rac1 inhibitor II and siRac1 inhibit EPS‐stimulated Akt phosphorylation on sites S473 and T308. Our findings implicate a Rac1‐Akt signaling pathway in EPS‐stimulated GLUT4 translocation in C2C12 myotubes.