Insulin resistance in H-35 rat hepatoma cells is mediated by post-receptor mechanisms.
Incubation of H-35 cells with 300 ng/ml (50 nM) of insulin causes a 3-4-fold induction of tyrosine aminotransferase at 4-6 h of incubation. At 24 h the activity of transaminase returns to basal levels despite the presence of sufficient insulin to stimulate a maximal response. Furthermore, addition of 300 ng/ml of fresh insulin fails to stimulate the induction of transaminase. In contrast, the addition of 0.1 microM dexamethasone to insulin-treated cells stimulates the induction of tyrosine aminotransferase, indicating that the loss of responsiveness is specific to insulin action. Incubation of H-35 cells with insulin also causes a 25-30% decrease in insulin binding. This modest decrease in receptor binding is not sufficient to explain the virtually complete loss of insulin responsiveness. Hence, in H-35 hepatoma cells insulin-induced desensitization to insulin action is mediated primarily by post-receptor events.
D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D007333:Insulin Resistance; D008114:Liver Neoplasms, Experimental / Q000503:physiopathology*; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects*; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D007328:Insulin; D014444:Tyrosine Transaminase; D011972:Receptor, Insulin