Fernando Escrivá

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 different 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 report that, in a serum-free condition and the presence of non-stimulatory doses of insulin, 5–20 mm glucose evoked an increase of IGF-I and -II mRNA abundance. 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 carbohydrate. The experiment with 2-deoxyglucose suggests that glucose 6-phosphate, but not its further metabolism, is necessary for the induction of IGF transcript abundance in cultured fetal hepatocytes. Finally, the glucose-induced rise in IGF-II mRNA, the main IGF in fetal stages, was mediated by stimulation of gene transcription and increased transcript stability. The results support the idea that IGFs belong to a family of genes that are positively regulated by glucose.

Effect of Growth Hormone on Liver Glycogen Accumulation in Suckling Rats

The regulation of liver glycogen turnover in the neonatal period differs from that of the adult state. Little is also known about the regulation exerted by GH in the first period of life. To shed light on the regulation of glycogen production and in particular to study the role of GH on liver glycogen accumulation, we investigated the effect of GH administration in control or GH-deficient neonatal rats. A slow-release GH preparation was injected subcutaneously on days 9 and 12 of life, in normal and neonatally treated rats with thyroxine or cortisol. Seventy-two hours after the last GH administration, liver glycogen was increased without concomitant elevation of plasma insulin and corticosterone levels and in addition without sequential inactivation of glycogen synthase. These data strongly suggest that the current concepts on the regulation of the hepatic synthesis of glycogen should be revised.