Mitogenic action of insulin: friend, foe or 'frenemy'?
Either endogenous or exogenous hyperinsulinaemia in the setting of insulin resistance promotes phosphorylation and activation of farnesyltransferase, a ubiquitous enzyme that farnesylates Ras proteins. Increased availability of farnesylated Ras at the plasma membrane enhances mitogenic responsiveness of cells to various growth factors, thus contributing to progression of cancer and atherosclerosis. This effect is specific to insulin, but is not related to the type of insulin used. The stimulatory effect of hyperinsulinaemia on farnesyltransferase in the presence of insulin resistance represents one potential mechanism responsible for mitogenicity and atherogenicity of insulin.
Adult Diabetes Program, University of Colorado Denver, Mail Stop 8106, 12631 E 17th Ave, Aurora, CO 80045, USA. Boris.Draznin@UCDenver.edu
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Draznin
D050197:Atherosclerosis / Q000209:etiology; D002455:Cell Division / Q000502:physiology; D003920:Diabetes Mellitus / Q000188:drug therapy; D051231:Farnesyltranstransferase / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000502:physiology* / Q000627:therapeutic use; D000069036:Insulin Glargine; D007333:Insulin Resistance / Q000502:physiology*; D049528:Insulin, Long-Acting; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology; D018631:ras Proteins / Q000378:metabolism
D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D051231:Farnesyltranstransferase; D018631:ras Proteins