Insulin modulates STAT3 protein activation and gene transcription in hepatic cells

Treatment of rat hepatoma cells with insulin attenuated the interleukin 6 (IL-6) stimulation of acute phase plasma protein genes, To identify the potential mechanism of this action, the influence of insulin on IL-6 signal transduction was determined, An insulin dose-dependent reduction in signal transducer and activator of transcription 3 (STAT3) gene transcription, mRNA accumulation, protein concentration, and IL-6-inducible DNA binding activity was detected, A reduction in the IL-6-activated sis-inducible element binding of STAT3 was observed within 4 h of insulin treatment, whereas a maximal 3-4-fold lower STAT protein concentration was measured after 8-24 h of insulin treatment. Insulin mediated a similar magnitude reduction in the amount of mRNA encoding the IL-6 receptor alpha subunit and IL-6 binding activity, These effects of insulin appear to contribute to the strongly suppressed transcriptional induction of the IL-6-responsive acute phase plasma protein genes.