Zucker lean and fatty rat hepatocytes respond differently to insulin and retinoids in the expression of glucose and lipid metabolic genes

Abstract

We found that retinoids synergized with insulin to induce glucokinase gene (Gck) expression in primary hepatocytes, indicating their roles in modulating insulin sensitivity. Whether any change of this synergy exists in insulin resistant animals is unknown. The expression levels of Gck, Srebf‐1c, Pck1 and Fas in hepatocytes isolated from Zucker lean (ZL, insulin sensitive) and fatty (ZF, insulin resistant) rats in response to increasing concentrations of all trans retinoic acid (RA) with or without 1 nM insulin were analyzed by real time PCR. For Gck, RA started to induce its expression at 0.1 uM and 3uM, and synergized with insulin in ZL and ZF hepatocytes, respectively. The Srebf‐1c mRNA was induced by RA at 0.1 uM and insulin in ZL, but not ZF hepatocytes. The Pck1 mRNA was induced by RA at 0.1uM or higher in both ZL and ZF hepatocytes. Insulin‐mediated suppression of Pck1 expression was attenuated by RA at 3uM in ZL, but not ZF cells. Fas mRNA was not affected by RA in both ZL and ZF hepatocytes after 6 hours of treatment. Our results showed that ZL and ZF hepatocytes respond differently to insulin and RA treatments, suggesting alterations of RA responses in liver of insulin resistant rats.Grant Funding Source: AHA