Molecular determinants of insulin action.
Insulin rapidly stimulates tyrosine phosphorylation of a 185-kDa protein in most cell types. This protein, insulin receptor substrate 1 (IRS-1), has been implicated as the first postreceptor step in insulin signal transmission based on studies with insulin receptor mutants. In cell culture and in vitro, phosphorylated IRS-1 associates with the lipid-metabolizing enzyme phosphatidylinositol 3-kinase (PI 3-kinase), resulting in activation of this enzyme. Thus, the insulin receptor, IRS-1 and PI-3 kinase represent three of the earliest steps in insulin action at the cellular level. We have recently demonstrated that insulin is capable of stimulating PI 3-kinase activity in liver and muscle in vivo in animals and that IRS-1 phosphorylation may play a significant role in the association/activation with PI 3-kinase in vivo.
Kahn
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Joslin Diabetes Center, Boston, Mass. 02215.
Folli
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D000818:Animals; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins / Q000378:metabolism; D019000:Phosphotyrosine; D011972:Receptor, Insulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D019000:Phosphotyrosine; D014443:Tyrosine; D011972:Receptor, Insulin