PHOSPHOENOLPYRUVATE CARBOXYKINASE IN EXPERIMENTAL INTRA-UTERINE GROWTH-RETARDATION IN RATS

The role of impaired gluconeogenesis in the pathogenesis of neonatal hypoglycemia in intrauterine growth retardation (IUGR) was examined. IUGR was produced experimentally in 8 pregnant rats by ligation of uterine arteries at the 17th day of gestation. Delivery occurred spontaneously at term. Sham operations were performed in 5 pregnant rats at the same gestational age and the fetuses delivered at term served as controls. The body wt of newborn rats with IUGR were significantly lower than the controls (5.32 .+-. 0.12 vs. 6.22 .+-. 0.06 g, mean .+-. SE, P < 0.001). The fetal liver wt were significantly smaller in IUGR than in the control animals (0.224 .+-. 0.14 vs. 0.340 .+-. 0.12 g, P < 0.001). The activity of phosphoenolpyruvate carboxykinase (PEPCK) (the rate-limiting enzyme of gluconeogenesis) in liver cytosols was significantly lower in rats with IUGR (0.06 .+-. 0.01 vs. 0.11 .+-. 0.02 .mu.M phosphoenolpyruvate/g liver per min when compared with controls (P < 0.05). A direct relationship between this enzyme and the birth wt was observed, suggesting a close relationship between intrauterine nutrition and the status of gluconeogenesis. The blood glucose level was lower in growth-retarded fetuses (36.6 .+-. 4.7 vs. 69.6 .+-. 4.3 mg/dl, P < 0.001) when compared with controls. Gluconeogenesis apparently is impaired in IUGR and is partly responsible for the increase in the incidence of neonatal hypoglycemia in this group of subjects.