title: Interaction between leptin and insulin signaling pathways differentially affects JAK-STAT and PI 3-kinase-mediated signaling in rat liver.
abstract: Chronic leptin treatment markedly enhances the effect of insulin on hepatic glucose production unproportionally with respect to body weight loss and increased insulin sensitivity. In the present study the cross-talk between insulin and leptin was evaluated in rat liver. Upon stimulation of JAK2 tyrosine phosphorylation, leptin induced JAK2 co-immunoprecipitation with STAT3, STAT5b, IRS-1 and IRS-2. This phenomenon parallels the leptin-induced tyrosine phosphorylation of STAT3, STAT5b, IRS-1 and IRS-2. Acutely injected insulin stimulated a mild increase in tyrosine phosphorylation of JAK2, STAT3 and STAT5b. Leptin was less effective than insulin in stimulating IRS phosphorylation and their association with PI 3-kinase. Simultaneous treatment with both hormones yielded no change in maximal phosphorylation of STAT3, IRS-1, IRS-2 and Akt, but led to a marked increase in tyrosine phosphorylation of JAK2 and STAT5b when compared with isolated administration of insulin or leptin. This indicates that there is a positive cross-talk between insulin and leptin signaling pathways at the level of JAK2 and STAT5b in rat liver.
authors.affiliation: Departamento de Clínica Médica, FCM, Universidade Estadual de Campinas, 13081-970 Campinas, SP, Brasil.
authors.forename: José B C
authors.initials: JB
authors.lastname: Carvalheira
authors.forename: Eliane B
authors.initials: EB
authors.lastname: Ribeiro
authors.forename: Franco
authors.initials: F
authors.lastname: Folli
authors.forename: Lício A
authors.initials: LA
authors.lastname: Velloso
authors.forename: Mario J A
authors.initials: MJ
authors.lastname: Saad
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D015151:Immunoblotting; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D020738:Leptin / Q000502:physiology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008894:Milk Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010750:Phosphoproteins / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014443:Tyrosine / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526296:Irs1 protein, rat; C526299:Irs2 protein, rat; D020738:Leptin; D008894:Milk Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494088:Stat3 protein, rat; C494097:Stat5b protein, rat; D015534:Trans-Activators; D014443:Tyrosine; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2