Insulin Antagonism of Dexamethasone-Induced Increase of Argininosuccinate Synthetase and Argininosuccinate Lyase Activities in Cultured Fetal Rat Liver

Abstract

In fetal rat liver explants maintained in organ culture, the addition of dexamethasone (4.6 × 10^––6M) produced a 2- to 3-fold increase in the activity of argininosuccinate synthetase and in argininosuccinate lyase after 24 and 48 h of incubation. Insulin (1.8 × 10^––6M) alone had no effect on the enzyme activities, but when incubated together with dexamethasone, it abolished the dexamethasone-induced increase of argininosuccinate synthetase and inhibited the argininosuccinate lyase activity by 80%, at 24 h. At 48 h, the inhibition of both enzyme activities was 68 %. The antagonistic effect of insulin on the dexamethasone action is discussed in relation to the mechanism of perinatal enzyme induction. Hyperinsulinemia may interfere with the development of enzyme systems during the perinatal period. This could have relevance in the care of infants of diabetic mothers.