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.
Singleton
J R
JR
Department of Neurology, University of Utah, Salt Lake City, Utah 84108, USA. rob.singleton@hsc.med.utah
Feldman
E L
EL
D000818:Animals; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000627:therapeutic use; D018482:Muscle, Skeletal / Q000378:metabolism*; D009135:Muscular Diseases / Q000188:drug therapy / Q000378:metabolism*
D007334:Insulin-Like Growth Factor I