Insulin modulates STAT3 protein activation and gene transcription in hepatic cells

J Biol Chem. 1996 Oct 4;271(40):24418-24. doi: 10.1074/jbc.271.40.24418.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Insulin / pharmacology*
  • Insulin Receptor Substrate Proteins
  • Interleukin-6 / metabolism
  • Intracellular Signaling Peptides and Proteins
  • Kinetics
  • Liver / drug effects*
  • Liver / metabolism
  • Phosphoproteins / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription, Genetic*
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • DNA-Binding Proteins
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • Irs1 protein, rat
  • Irs2 protein, rat
  • Phosphoproteins
  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Trans-Activators