title: Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates.
abstract: Tumor necrosis factor-alpha (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 nM TNF for 1 h led to a 65% decrease in insulin-induced tyrosine phosphorylation of both the insulin receptor beta-subunit and IRS-1, its major cytosolic substrate. TNF-induced impairment of tyrosine phosphorylation was maximal at 0.5 nM 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.
authors.affiliation: Institute of Endocrinology, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: R
authors.initials: R
authors.lastname: Feinstein
authors.forename: H
authors.initials: H
authors.lastname: Kanety
authors.forename: M Z
authors.initials: MZ
authors.lastname: Papa
authors.forename: B
authors.initials: B
authors.lastname: Lunenfeld
authors.forename: A
authors.initials: A
authors.lastname: Karasik
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D007328:Insulin / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D011972:Receptor, Insulin