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 α 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.