EFFECTS OF INSULIN, EPINEPHRINE, AND GLUCOSE ON REGULATION OF TRANSCRIPTION OF THE SERINE DEHYDRATASE GENE IN NEWBORN DOGS

Our previous investigations showed that hyperinsulinemia incompletely suppressed the transcription of the gene encoding L-serine dehydratase (SDH) (EC 4.2.1.13), a gluconeogenic enzyme, in newborn dogs. To test another hypothesis that insulin resistance in newborn mammals may be partially due to counterregulatory factors, such as epinephrine, eugly cemic hyperinsulinemic clamps, hyperglycemic hyperinsulinemic clamps, and hyperglycemic hyperinsulinemic hyperepinephrinemic clamps were per formed in newborn dogs in the present study. The infusion rates of ins ulin and epinephrine were 30 mU/kg/min and 150 ng/kg/min, respectively ; the glucose infusion rate was adjustable. The SDH mRNA levels in kid ney and liver of newborn dogs were quantitatively analyzed by using ra t SDH cDNA probe and by a personal densitometer. The results showed th at insulin, glucose, and epinephrine did not change the kidney SDH mRN A level; hyperinsulinemia and hyperglycemia reduced the liver SDH mRNA level by 8.5 and 29.2%, respectively; in the presence of hyperglycemi a and hyperinsulinemia, epinephrine was able to increase the liver SDH mRNA by 27.8%, almost offsetting the reduction of the liver SDH mRNA level induced by the combination of insulin and glucose. We conclude t hat the enhanced regulatory effect of epinephrine counteracting insuli n on SDH gene transcription in liver of newborn dogs may be one of the mechanisms responsible for the neonatal insulin resistance which cont ributes to neonatal hyperglycemia. (C) 1996 Academic Press, Inc.