INSULIN-RESISTANCE AND THE TRANSCRIPTION OF THE GLUCOSE-6-PHOSPHATASEGENE IN NEWBORN DOGS

In the present report changes in the mRNA level of glucose-6-phosphata se (G6Pase; EC 3.1.39) in newborn and adult dogs in vivo were studied to further test the hypotheses that neonatal hyperglycemia may be due to unsuppressed gluconeogenesis by insulin and that the antidiabetic r ole of insulin-like growth factor-1 (IGF-1) may be intact in newborn d ogs who have consistently demonstrated insulin resistance. Our results were the following: (i) Both renal and hepatic G6Pase mRNA were expre ssed at birth and increased with time during a 24-h period of fasting after birth. (ii) The renal G6Pase mRNA levels in newborn dogs did not respond to either insulin or epinephrine. (iii) Hyperinsulinemia lowe red the liver G6Pase mRNA by only 16.3% in newborn dogs, but reduced t he liver G6Pase mRNA to an undetectable level in adult dogs. (iv) Hype rglycemia decreased the hepatic G6Pase mRNA by 14.3% in newborn dogs u nder hyperinsulinemia. (v) Infused epinephrine did not elevate the hep atic G6Pase mRNA level in newborn dogs in the presence of hyperglycemi a and hyperinsulinemia. (vi) In newborn dogs, hyper-IGF-l rapidly redu ced the hepatic G6Pase mRNA level by 50%, and hypoglycemia was unable to elevate the hepatic G6Pase mRNA level under the hyper-IGF-l. We con cluded that the reduced rate of suppression of transcription of the li ver G6Pase gene by insulin in newborn dogs may reflect the unsuppresse d neonatal hepatic gluconeogenesis due to insulin resistance and that the physiological roles of IGF-1 seemed to be intact in newborn dogs a nd may be not responsible for neonatal hyperglycemia. (C) 1997 Academi c Press.