Endocrine Abstracts

Hepatic glucose metabolism is zonated. Glycolysis is mainly localized in hepatocytes surrounding the hepatic vein (pericentral zone) whereas gluconeogenesis is mainly carried out by hepatocytes surrounding the portal vein (periportal zone). Expression of the gene encoding the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK, PCK1) is reduced upon feeding, an effect mainly controlled by insulin. PEPCK is considered a peri-portal enzyme. However, the differential effects of feeding and fasting and thus changes in plasma insulin concentrations on PEPCK zonation are unknown. In the present study, laserdissection microscopy, immunohistochemistry and primary periportal and pericentral hepatocytes were used to assess the effects of feeding and fasting on PEPCK gene and protein zonation. The reduced hepatic Pepck mRNA concentrations in fed mice resulted in reduced PEPCK protein expression in pericentral but not in periportal hepatocytes. In alloxan-induced type 1 diabetic mice, which lack insulin, Pepck mRNA expression and PEPCK protein levels did not increase upon fasting, confirming the regulatory role of insulin. Nevertheless, PEPCK was still zonated along the liver acinus suggesting that other factors than insulin mediate PEPCK zonation. In conclusion, our data show that the feeding to fasting response affects PEPCK protein expression and this is mediated by insulin. This transition mostly affects pericentral hepatocytes. However, not insulin but other yet to be determined factor(s) regulate PEPCK zonation along the liver acinus.