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Updated: May 18, 2026

Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
AMP-activated protein kinase stimulates myostatin expression in C2C12 cells
Arun K Das1, Qi-Yuan Yang, Xing Fu
1Department of Animal Sciences, Washington State University, Pullman, WA 99164, USA.
Abstract:
AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism in skeletal muscle; AMPK induces muscle protein degradation but the underlying mechanisms are unclear. Myostatin is a powerful negative regulator of skeletal muscle mass and growth in mammalian species. We hypothesized that AMPK stimulates myostatin expression, which provides an explanation for the negative role of AMPK in muscle growth. The objective of this study is to demonstrate that AMPK stimulates myostatin expression using C2C12 cells as a model. Activation of AMPK by 5-aminoimidazole-4-carboxamide-1-β-d-riboruranoside (AICAR) dramatically increased the mRNA expression and protein content of myostatin in C2C12 myotubes, and to a lesser degree in myoblasts. Metformin, another AMPK activator, also stimulated myostatin expression at low concentrations. In addition, ectopic expression of AMPK wild-type α subunit (enhancing AMPK activity) and AMPK K45R mutant (knockdown AMPK activity) enhanced and reduced myostatin expression, respectively. These results indicate that AMPK stimulates myostatin expression in C2C12 cells, providing an explanation for the negative effect of AMPK on muscle growth.
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