Zucker fatty rat hepatocytes have impaired regulation of gene expression mediated by insulin and retinoids

Abstract

The mechanism of insulin resistance at gene expression level is still unrevealed. We demonstrated retinoids synergize with insulin (INS) to induce glucokinase (Gck) expression in primary hepatocytes, showing their roles in modulating insulin action. Herein, we compared the responses of Gck, Srebf‐1c, Pck1 and Pklr in hepatocytes isolated from Zucker lean (ZL) and fatty (ZF) rats to INS (0 to 100nM) without or with 5 uM all trans retinoic acid (RA). The mRNA levels of these genes were analyzed by real time PCR. For Gck, RA started to synergize with INS at 1nM to induce its expression in ZL and ZF hepatocytes, but the induction folds by INS were higher in ZL than in ZF cells with or without RA. The Srebf‐1c mRNA was only induced in ZL, but not ZF hepatocytes. The Pck1 mRNA levels were decreased more in ZL than in ZF cells by 1 and 10nM INS without RA, and by 1nM INS with RA. The Pklr mRNA level was higher in ZF cells at basal state. It was not responsive to INS, RA or INS + RA in both ZL and ZF hepatocytes. We showed here ZL hepatocytes respond to INS and RA more robustly in regulation of gene expression than ZF cells, suggesting a potential model to study insulin resistance at gene expression level.Grant Funding Source: American Heart Association