Insulin-like growth factor-I in muscle metabolism and myotherapies

The critical anabolic and trophic role of signaling by insulin-like growth factors (IGF) I and II via the type-I IGF receptor (IGF-IR) is reviewed throughout the life of skeletal myocytes. The proliferative effects of IGF-IR stimulation, both during embryogenesis and during satellite cell proliferation following denervation or muscle injury, are mediated primarily through activation of mitogen-activated protein kinases. Signaling through phosphatidylinositol 3-kinase is essential to muscle protein synthesis and glucose uptake and may contribute to the observed resilience of mature muscle to programmed cell death. Degeneration or inhibition of the GH-IGF-I axis by aging, cachexia, sepsis, diabetes, drugs, and disuse all enhance muscle catabolism, and opposition of these effects by IGF-I may form the basis of effective myotherapy. (C) 2001 Academic Press.