Fig. 5.

Mechanisms for inhibition of atrophy and growth promotion by muscle activity. With repeated muscle contractions, IGF-1 production by the muscle increases, which stimulates protein synthesis and fiber hypertrophy through activation of PI3K and AKT kinases. AKT also causes phosphorylation and nuclear exclusion of FoxO 1, 3, and 4, which suppresses atrogene expression and proteolysis. In addition, PGC-1α is induced, leading to increased production of mitochondria and a shift to slow-twitch, oxidative fibers. PGC-1α also inhibits transcriptional activity of FoxO3, which suppresses atrogene expression and protein degradation.