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Details for phenotype: negative regulation of insulin receptor signaling pathway

EndoNet ID: ENP00155

Name

negative regulation of insulin receptor signaling pathway

General information

This phenotype is not pathologic

Links to other resources

GO
MeSH term 68011972

Phenotype triggers

  • normal activity of leptin receptor
    in adipose_tissue
    • Leptin inhibits insulin receptor signaling in cultured cells. [1]
  • normal activity of TNFR1
    in adipose_tissue
    • TNF-alpha inhibits insulin receptor signaling in cultured cells. [1]
    • TNF-α inhibits insulin signaling via stimulation of p55 TNFR and sphingomyelinase activity, which results in the production of an inhibitory form of insulin receptor substrate-1 . [2]
  • normal activity of leptin receptor
    in hepatocyte
    • Exposure of hepatic cells to leptin, at concentrations comparable with those present in obese individuals, caused attenuation of several insulin-induced activities, including tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), association of the adapter molecule growth factor receptor-bound protein 2 with IRS-1, and down-regulation of gluconeogenesis. In contrast, leptin increased the activity of IRS-1-associated phosphatidylinositol 3-kinase. These in vitro studies raise the possibility that leptin modulates insulin activities in obese individuals. [3]
Reference