Regulation of insulin-like growth factor-I and -II by glucose in primary cultures of fetal rat hepatocytes

A selective primary culture of fetal rat hepatocytes was established in our laboratory in order to elucidate the molecular mechanisms of action of dif ferent factors and conditions on insulin-like growth factor (IGF)-I and -II gene expression during the perinatal period of the rat, In this model we r eport that, in a serum-free condition and the presence of non-stimulatory d oses of insulin, 5-20 mM glucose evoked an increase of IGF-I and -II mRNA a bundance, Glucose regulated in a parallel manner IGF peptide secretion, and an excellent correlation was observed between IGF-I and -II mRNA and IGF-I and -II peptide levels in the conditioned media in response to the carbohy drate. The experiment with 2-deoxyglucose suggests that glucose 6-phosphate , but not its further metabolism, is necessary for the induction of IGF tra nscript abundance in cultured fetal hepatocytes. Finally, the glucose-induc ed rise in IGF-II mRNA, the main IGF in fetal stages, was mediated by stimu lation of gene transcription and increased transcript stability. The result s support the idea that IGFs belong to a family of genes that are positivel y regulated by glucose.