title: Discrimination between signaling pathways in regulation of specific gene expression by insulin and growth hormone in hepatocytes.
abstract: Insulin and GH can activate common signaling elements in many tissues and cell lines. We investigated the possibility of overlap in signaling pathways activated by insulin and GH in a key target cell, the hepatocyte. In primary cultures of rat hepatocytes, GH caused a dose- and time-dependent increase in tyrosine phosphorylation of signal transducer and activator of transcription 5. This was accompanied by the induction of the mRNA encoding suppressor of cytokine signaling 2. Neither of these effects took place in companion hepatocytes challenged with insulin. By contrast, insulin caused a rapid and sustained phosphorylation of protein kinase B, accompanied by a massive induction of the mRNA encoding glucokinase. GH had no detectable effect on phosphorylation of protein kinase B or level of glucokinase mRNA. Insulin also elicited brief hyperphosphorylation of ERK1 and 2, an effect not seen in GH-stimulated hepatocytes. Thus, there was a clear demarcation of signaling events triggered in hepatocytes by insulin and GH, and this was accompanied by hormone-specific responses with respect to the induction of gene expression. Additionally, the current results show that signal transducer and activator of transcription 5 activation is neither necessary nor sufficient for the insulin-dependent induction of hepatic glucokinase.
authors.affiliation: Division of Clinical Biochemistry and Experimental Diabetes Research, University of Geneva School of Medicine, Switzerland.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ribaux
authors.forename: Asllan
authors.initials: A
authors.lastname: Gjinovci
authors.forename: Henry B
authors.initials: HB
authors.lastname: Sadowski
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Iynedjian
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology*; D005941:Glucokinase / Q000235:genetics; D013006:Growth Hormone / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008894:Milk Proteins; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D007328:Insulin; D008894:Milk Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D050799:STAT5 Transcription Factor; C491408:Socs2 protein, rat; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D013006:Growth Hormone; D005941:Glucokinase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt