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