Insulin hyperresponsiveness in partially hepatectomized diabetic rats.
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.
Carrillo
M C
MC
Instituto de Fisiología Experimental, CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina. ifise1@citynet.net.ar
Favre
C
C
Monti
J A
JA
Alvarez
M L
ML
Carnovale
C E
CE
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
D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526296:Irs1 protein, rat; D010750:Phosphoproteins; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D011972:Receptor, Insulin