TRANSCRIPTION OF HEPATIC CYTOSOLIC PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE IN NEWBORN DOGS

Physiological studies hypothesized that unsuppressed gluconeogenesis b y insulin in newborn dogs may be a mechanism responsible for neonatal hyperglycemia. In the present study, we determined the effects of fast ing and the infusion of insulin glucose, and/or epinephrine on the liv er cytosolic mRNA levels of the gene for the key regulatory enzyme of gluconeogenesis, phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32 ), in newborn dogs in vivo to further test the hypothesis. We observed the following: (i) Fasting increased the hepatic PEPCK mRNA level in newborn dogs. The hepatic PEPCK mRNA level was not detectable at birth ; the PEPCK mRNA level at 4 h was arbitrarily determined as 100.0 +/- 27.8%, was 108.1 +/- 18.4% at 10 h, and stayed at the same level at 24 h (109.1 +/- 8.2). (ii) Euglycemic hyperinsulinemia did not significa ntly reduce the hepatic PEPCK mRNA levels in newborn dogs; however, th e same treatment resulted in the repression of the liver PEPCK mRNA to undetectable levels in adult dogs. (iii) Under hyperinsulinemia, a mo derate hyperglycemia lowered the liver PEPCK mRNA in newborn dogs to u ndetectable levels. (iv) In newborn dogs, despite the presence of hype rinsulinemia and hyperglycemia, the infused epinephrine was still able to elevate the liver PEPCK mRNA from undetectable levels to 79% of th e control levels. We suggest that unsuppressed neonatal gluconeogenesi s in the presence of hyperinsulinemia may be evidence of insulin resis tance in newborn dogs and that the stimulatory effect of epinephrine o n gluconeogenesis overriding insulin and glucose in the liver of the n ewborn dogs may be a mechanism for inducing neonatal hyperglycemia. (C ) 1996 Academic Press, Inc.