Characterization of insulin sensitivity and signaling in adipocytes from congenic rats.

SUMMARY Genetic analysis of the diabetic Goto-Kakizaki rat has identified a major diabetes quantitative trait locus (Niddm1). Congenic strains generated for two different subloci, Niddm1f and Niddm1i, show defects in insulin action and secretion, respectively. In this work, we demonstrated that insulin-induced lipo genesis and phosphorylation of protein kinase B are reduced in adipocytes from Niddm1f rats as compared to adipocytes from control F344 rats. On the other hand, tyrosine phosphorylation of insulin receptor substrate 1 and serine phosphorylation of acetyl coenzyme A carboxylase were similar in both strains. In contrast to the results on Niddm1f adipocytes, insulin-induced lipogenesis in adipocytes from Niddm1i rats was increased. In summary, adipocytes from Niddm1f rats show insulin resistance, whereas adipocytes from Niddm1i rats show improved insulin action when comparing to F344 rats. Defect phosphorylation of protein kinase B most likely contributes to insulin resistance in Niddm1f adipocytes.