Insulin hyperresponsiveness in partially hepatectomized diabetic rats

The present work analyzes the expression of insulin receptors and theirs re lated intracellular signaling molecules in partially hepatectomized-diabeti c rats. Insulin binding through Scatchard analysis was studied using isolat ed hepatocytes of Control (Sham-operated), Hepatectomized, Diabetic and Dia betic-Hepatectomized male Wister rats. In a set of in vivo experiments, the levels of or subunit of the insulin receptor, the insulin receptor substra te 1 (IRS-I) and the phosphatidylinositol 3-kinase (PI3K) were determined, [H-3]-thymidine incorporation into DNA 24 or 48 h after surgery was assesse d in all the experimental groups. Scatchard analysis showed that insulin re ceptor number was increased in diabetic and in hepatectomized rats in the s ame extent (64%, with respect to Controls). Diabetic-hepatectomized rats sh owed a dramatic increase of the receptor concentration (400%) and on the af finity constant (532%). Besides, the insulin receptor expression was increa sed in the treated groups, being the higher values those of the diabetic-he patectomized rats. IRS-1 and PI3K showed similar increases. DNA synthesis w as not impaired by the diabetes state. In conclusion, increased expression of IR and IRS-I leads to increased association of PI3K in vivo in diabetic regenerating rats. The enhancement of this pathway may reveal an insulin hy perresponsiveness in these animals. (C) 2001 Elsevier Science Inc. All righ ts reserved.