The inhibitory effect of glucose on phosphoenolpyruvate carboxykinase geneexpression in cultured hepatocytes is transcriptional and requires glucosemetabolism

Phosphoenolpyruvate carboxykinase (PEPCK) is the rate-limiting enzyme of gl uconeogenesis in the liver. PEPCK gene expression is controlled at the tran scriptional level and is mainly regulated by hormones that are involved in glucose homeostasis, In this study, we have investigated the role of glucos e on PEPCK gene expression in cultured hepatocytes. We demonstrate that glu cose counteracts the stimulatory effect of glucocorticoids and cAMP on PEPC K expression, Glucose must be metabolized through glucokinase to have its i nhibitory effect, The effect of glucose is mainly transcriptional and the r egion responsible for glucose inhibition is localized in the first 490 bp o f the promoter. (C) 1999 Federation of European Biochemical Societies.