Tumor necrosis factor-alpha suppresses insulin-induced tyrosine phosphorylation of insulin receptor and its substrates
| Autor: | Bruno Lunenfeld, R Feinstein, Avraham Karasik, Moshe Z. Papa, Hannah Kanety |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
medicine.medical_specialty
Cell Survival medicine.medical_treatment Biology Biochemistry Receptor tyrosine kinase chemistry.chemical_compound Liver Neoplasms Experimental Insulin resistance Internal medicine Insulin receptor substrate Tumor Cells Cultured medicine Animals Insulin Phosphorylation Molecular Biology Tumor Necrosis Factor-alpha Tyrosine phosphorylation Cell Biology medicine.disease Receptor Insulin IRS2 Rats Insulin receptor Endocrinology chemistry biology.protein Tyrosine Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 268:26055-26058 |
| ISSN: | 0021-9258 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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