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.
Campos
S P
SP
Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, New York 14263, USA.
Wang
Y
Y
Baumann
H
H
D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018123:Receptors, Interleukin / Q000235:genetics; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D004268:DNA-Binding Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D010750:Phosphoproteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D015534:Trans-Activators