D-glucose regulates maintenance and function of pancreatic beta-cells. Several studies have shown that IRS-2, but not IRS-1, is necessary to maintain and sufficient to expand functional beta-cell mass. We therefore analyzed the expression of IRS-2 and IRS-1 in beta-cells after culture in the presence of various concentrations of D-glucose and other metabolisable or non-metabolisable hexoses. D-...

Insulin receptor substrate (IRS) molecules are key mediators in insulin signaling and play a central role in maintaining basic cellular functions such as growth, survival, and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this f...

OBJECTIVE Polycystic ovary syndrome (PCOS) is a common endocrinologic disease in women. In the present study, we examined the relationship of the IRS-1 Gly972Arg and IRS-2 Gly1057Asp polymorphisms to PCOS and phenotypic features of PCOS in a Chinese population from Taiwan. MATERIALS AND METHODS A total of three hundred and forty genetically unrelated women with age from 18 to 45 years, includ...

Organ weight was compared in adult mice with deletion of one (IRS-1) or both (IRS-1) copies of the insulin receptor substrate-1 (IRS-1) gene and IRS-1 littermates. IRS-1 mice showed modest reductions in weight of most organs in proportion to a decrease in body weight. IRS-1 mice showed major reductions in weight of heart, liver, and spleen that were directly proportional to a decrease in body w...

The phosphorylation of insulin receptor substrate 1 (IRS-1) on tyrosine residues by the insulin receptor (IR) tyrosine kinase is involved in most of the biological responses of insulin. IRS-1 mediates insulin signaling by recruiting SH2 proteins through its multiple tyrosine phosphorylation sites. The phosphorylation of IRS-1 on serine/threonine residues also occurs in cells; however, the parti...

Integrins are transmembrane receptors involved in interactions between cells and extracellular matrix proteins. Here we show that cell adhesion regulates insulin receptor substrate-1 (IRS-1) mRNA synthesis. When fibroblasts are held in suspension, lower levels of IRS-1 mRNA, but not of IRS-2 mRNA, are detected, and this effect is due to the negative regulation of IRS-1 transcription rather than...

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the phosphorylation of its cytosolic substrate, insulin receptor substrate-1 (IRS-1) which, in turn, associates with proteins containing SH2 domains. It has been shown that IRS-1 associates with the tyrosine phosphatase SHPTP2 in cell cultures. While the effect of the IRS-1/SHPTP2 association on insulin signal transduc...

Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by the insulin receptor permits this docking protein to interact with signaling proteins that promote insulin action. Serine phosphorylation uncouples IRS-1 from the insulin receptor, thereby inhibiting its tyrosine phosphorylation and insulin signaling. For this reason, there is great interest in identifying serine/threonine kina...

The insulin receptor substrate-1 (IRS-1), a docking protein for both the type 1 insulin-like growth factor receptor (IGF-IR) and the insulin receptor, is known to send a mitogenic, anti-apoptotic, and anti-differentiation signal. Several micro RNAs (miRs) are suggested by the data base as possible candidates for targeting IRS-1. We show here that one of the miRs predicted by the data base, miR1...

Insulin receptor substrates (IRS-1 and -2) are essential for intracellular signaling by insulin and IGF-I, anabolic regulators of bone metabolism. Mice lacking the IRS-1 gene IRS-1(-/-) showed severe osteopenia with low bone turnover. IRS-1 was expressed in osteoblasts, but not in osteoclasts, of wild-type (WT) mice. IRS-1(-/-) osteoblasts treated with insulin or IGF-I failed to induce tyrosine...