Myostatin regulates glucose metabolism via the AMP-activated protein kinase pathway in skeletal muscle cells.
Myostatin (Mstn) is a secreted growth factor predominately expressed in skeletal muscle that negatively regulates skeletal muscle mass. Recent studies have indicated that loss function of myostatin not only increases muscle mass but also improves insulin sensitivity in vivo. In the present report, we demonstrated that myostatin regulates glucose metabolism by promoting glucose consumption and glucose uptake, increasing glycolysis, and inhibiting glycogen synthesis in skeletal muscle cells. Microarray analysis revealed that myostatin upregulates several genes involved in regulating glucose metabolism such as Glut1, Glut4, Hk2, and IL-6. Further investigation of the molecular basis of these phenomena revealed that AMP-activated protein kinase (AMPK), a key component for maintaining energy homeostasis, was activated by myostatin for promotion of glycolysis. Taken together, these findings provide the first experimental evidence that myostatin regulates glucose metabolism through the AMPK signal pathway in muscle cells. Importantly, our findings highlight that continued investigation of the metabolic function of myostatin is necessary for a comprehensive understanding of its active role in the regulation of skeletal muscle energy metabolism.
Chen
Yuewen
Y
The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, PR China.
Ye
Jianwei
J
Cao
Lingzhi
L
Zhang
Yong
Y
Xia
Weibo
W
Zhu
Dahai
D
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis; D006019:Glycolysis / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D055435:Myostatin / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D007328:Insulin; D055435:Myostatin; D006003:Glycogen; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases; D005947:Glucose