Electrical pulse stimulation induces GLUT4 translocation in a Rac-Akt-dependent manner in C2C12 myotubes

被引:31
作者
Hu, Fang [1 ]
Li, Nana [1 ]
Li, Zhu [1 ]
Zhang, Chang [1 ]
Yue, Yingying [1 ]
Liu, Qian [1 ]
Chen, Liming [1 ]
Bilan, Philip J. [2 ]
Niu, Wenyan [1 ]
机构
[1] Tianjin Med Univ, Tianjin Metab Dis Hosp, Tianjin Key Lab Metab Dis, Minist Educ,Dept Immunol,Key Lab Immune Microenvi, Tianjin 300070, Peoples R China
[2] Hosp Sick Children, Cell Biol Program, Toronto, ON, Canada
基金
中国国家自然科学基金;
关键词
Akt; C2C12; contraction; electrical pulse stimulation; GLUT4; Rac1; ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE CELLS; SMALL GTPASE RAC1; INDUCED INSULIN-RESISTANCE; GLUCOSE-UPTAKE; CONTRACTION REGULATION; ACTIN CYTOSKELETON; EXERCISE; TRANSPORT; PHOSPHORYLATION;
D O I
10.1002/1873-3468.12982
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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.
引用
收藏
页码:644 / 654
页数:11
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