[The expression of the insulin receptor substrate-1 (IRS-1) and analysis of its mechanism].
IRS-1 (insulin receptor substrate-1) is a major substrate for the insulin receptor tyrosine kinase. After phosphorylation by the insulin receptor, IRS-1 binds to the specific molecules which possess SH2 (src homology 2) domain such as 85 kDa subunit of phosphatidylinositol 3 kinase and may mediate insulin signals. The regulation of IRS-1 has been analyzed in animal models of insulin resistance, and its mechanism has been studied in culture cells. In animal models of insulin resistance, phosphorylation of IRS-1 was mainly regulated by the insulin receptor tyrosine kinase both in liver and muscle. However, IRS-1 protein level was differently regulated in muscle and liver. In muscle, IRS-1 protein decreased with dexamethasone treatment and in hypoinsulinemic states such as starvation and streptozotosine-induced diabetes and showed no change in hyperinsulinemic states such as obesity. In liver, IRS-1 protein increased with dexamethasone treatment and hypoinsulinemic states and decreased in hyperinsulinemic states. In cultured cell such as 3T3-L1 or 3T3-F442A adipocytes, IRS-1 was negatively regulated both by insulin and dexamethasone by different mechanisms. Insulin regulates the IRS-1 expression at protein level mainly by decreasing the half life of IRS-1 protein, and dexamethasone regulates it at mRNA level mainly by decreasing the half life of IRS-1 mRNA.
Shichiri
M
M
Department of Metabolic Medicine, Kumamoto University School of Medicine.
Araki
E
E
D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin
D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin