title: Insulin hyperresponsiveness in partially hepatectomized diabetic rats.
abstract: The present work analyzes the expression of insulin receptors and theirs related intracellular signaling molecules in partially hepatectomized-diabetic rats. Insulin binding through Scatchard analysis was studied using isolated hepatocytes of Control (Sham-operated), Hepatectomized, Diabetic and Diabetic-Hepatectomized male Wistar rats. In a set of in vivo experiments, the levels of alpha subunit of the insulin receptor, the insulin receptor substrate 1 (IRS-1) and the phosphatidylinositol 3-kinase (PI3K) were determined. [3H]-thymidine incorporation into DNA 24 or 48 h after surgery was assessed in all the experimental groups. Scatchard analysis showed that insulin receptor number was increased in diabetic and in hepatectomized rats in the same extent (64%, with respect to Controls). Diabetic-hepatectomized rats showed a dramatic increase of the receptor concentration (400%) and on the affinity constant (532%). Besides, the insulin receptor expression was increased in the treated groups, being the higher values those of the diabetic-hepatectomized rats. IRS-1 and PI3K showed similar increases. DNA synthesis was not impaired by the diabetes state. In conclusion, increased expression of IR and IRS-1 leads to increased association of PI3K in vivo in diabetic regenerating rats. The enhancement of this pathway may reveal an insulin hyperresponsiveness in these animals.
authors.affiliation: Instituto de Fisiología Experimental, CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina. ifise1@citynet.net.ar
authors.forename: M C
authors.initials: MC
authors.lastname: Carrillo
authors.forename: C
authors.initials: C
authors.lastname: Favre
authors.forename: J A
authors.initials: JA
authors.lastname: Monti
authors.forename: M L
authors.initials: ML
authors.lastname: Alvarez
authors.forename: C E
authors.initials: CE
authors.lastname: Carnovale
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002452:Cell Count; D002470:Cell Survival; D004247:DNA / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D008115:Liver Regeneration; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000378:metabolism
chemical_list: D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin