Tumor necrosis factor-α suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates

Revital Feinstein, Hannah Kanety, Moshe Z. Papa, Bruno Lunenfeld, Avraham Karasik

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    488 Scopus citations

    Abstract

    Tumor necrosis factor-α (TNF) has recently been shown to induce insulin resistance. We have examined the possible effect of TNF on the early events in insulin transmembrane signaling. Incubation of the insulin-sensitive rat hepatoma Fao cells with 5 UM TNF for 1 h led to a 65% decrease in insulin-induced tyrosine phosphorylation of both the insulin receptor ß-subunit and IRS-1, its major cytosolic substrate. TNF-induced impairment of tyrosine phosphorylation was maximal at 0.5 UM and was not accompanied by any reduction in insulin binding. Sixteen hours of TNF incubation led to further impairment in insulin-induced tyrosine phosphorylation of these proteins. Our findings suggest that TNF may exert its anti-insulin effect by interrupting the early insulin-stimulated tyrosine phosphorylation events, which are crucial to insulin transmembrane signaling.

    Original languageEnglish
    Pages (from-to)26055-26058
    Number of pages4
    JournalJournal of Biological Chemistry
    Volume268
    Issue number35
    StatePublished - 15 Dec 1993

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