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Diabet Med. 1996 Sep;13(9 Suppl 6):S103-8.

Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1 and identification of insulin receptor substrate-2.

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Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.


To clarify the physiological roles of insulin receptor substrate-1 (IRS-1) in vivo, we made mice with a targeted disruption of the IRS-1 gene locus. Mice homozygous for targeted disruption of the IRS-1 gene were born alive but were retarded in embryonal and postnatal growth. They also had resistance to the glucose-lowering effects of insulin, insulin-like growth factor-1 (IGF-1) and factor-2 (IGF-2). These data suggest the existence of both IRS-1-dependent and IRS-1-independent pathways for signal transduction of insulin and IGFs. Moreover, we identified tyrosine phosphorylation of a 190-kDa protein (pp 190) as a novel substrate (IRS-2) for insulin receptor kinase in livers of IRS-1 deficient mice which can bind both P13-kinase and Ash/Grb2.

[Indexed for MEDLINE]

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