Hormonal regulation of liver phosphoenolpyruvate carboxykinase and glucokinase gene expression at weaning in the rat.

During the suckling period, the rats are fed continuously with milk, which is a high-fat low-carbohydrate diet (HF). At weaning, milk is progressively replaced by the rat's laboratory chow which is a high-carbohydrate low-fat diet (HCHO), and this is accompanied by large hormonal modifications: an increase in plasma insulin and a decrease in plasma glucagon concentrations, and by marked changes in metabolic pathways in liver: decrease in hepatic gluconeogenesis and increase in glycolysis and lipogenesis. Most of the data concerning these changes are related to maximal activity of enzymes. The recent availability of specific cDNA probes for phosphoenolpyruvate carboxykinase (PEPCK), and glucokinase (GK) has allowed the study of the role of pancreatic hormones and nutrition in the changes of the expression of these genes at weaning in the rat. Regarding phosphoenolpyruvate carboxykinase gene transcription, the concentration of mRNA as well as the activity of PEPCK are elevated in the liver of suckling rat until the onset of weaning, 21 d after delivery. After weaning to a HCHO diet, both mRNA and activity of PEPCK rapidly decrease to a very low level. In contrast, weaning on an HF diet, which maintains high plasma glucagon and low plasma insulin levels, does not decrease in plasma glucagon concentration and a 90% decrease in PEPCK gene transcription and PEPCK mRNA concentration in 1 h. Regarding glucokinase gene transcription, the concentration of mRNA as well as the activity of GK are not detectable before 15 d after birth in the liver of the rat. They markedly increase when the newborn are weaned on an HCHO diet but not when they are weaned on an HF diet.(ABSTRACT TRUNCATED AT 250 WORDS)