胰岛素抵抗
胰岛素受体
内科学
内分泌学
胰岛素受体底物
酪氨酸激酶
IRS2
胰岛素
IRS1
肿瘤坏死因子α
化学
生物
受体
医学
作者
Gökhan S. Hotamisligil,Pascal Peraldi,Adriane I. Budavari,Ramsey Ellis,Morris F. White,Bruce M. Spiegelman
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:1996-02-02
卷期号:271 (5249): 665-670
被引量:2419
标识
DOI:10.1126/science.271.5249.665
摘要
Tumor necrosis factor-α (TNF-α) is an important mediator of insulin resistance in obesity and diabetes through its ability to decrease the tyrosine kinase activity of the insulin receptor (IR). Treatment of cultured murine adipocytes with TNF-α was shown to induce serine phosphorylation of insulin receptor substrate 1 (IRS-1) and convert IRS-1 into an inhibitor of the IR tyrosine kinase activity in vitro. Myeloid 32D cells, which lack endogenous IRS-1, were resistant to TNF-α-mediated inhibition of IR signaling, whereas transfected 32D cells that express IRS-1 were very sensitive to this effect of TNF-α. An inhibitory form of IRS-1 was observed in muscle and fat tissues from obese rats. These results indicate that TNF-α induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling.
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