DEVELOPMENTAL ASPECTS OF TRANSCRIPTION OF FRUCTOSE-1,6-BISPHOSPHATASEIN NEWBORN DOGS

Our previous investigations demonstrated that unsuppressed gluconeogen esis under hyperinsulinemia in newborn dogs may be a mechanism of neon atal hyperglycemia. In the present study, the transcription of the gen e for fructose-1,6-bisphosphatase (fru-1,6-P(2)ase; E 3.1.3.11) of new born dogs was studied under various metabolic perturbations (age, suck ling, fasting, and hyperinsulinemia). Total RNAs isolated from livers and kidneys were hybridized with a rat fru-1,6-P(2)ase cDNA probe. We observed that (i) fru-1,6-P(2)ase mRNA was expressed in Booth kidney a nd liver at birth and was about 40 and 80% of those in kidney and live r of adult dog, respectively; (ii) suckling decreased the kidney fru-1 ,6-P(2)ase mRNA level to 77.8 +/- 1.7% (24 h) from 100.0 +/- 8.0% (4 h ), but increased liver mRNA to 158.6 +/- 11.4% (24 h) from 100.0 +/- 2 .3% (4 h); (iii) during a 24-h period of fasting, the kidney fru-4,6-P (2)ase mRNA level did mot change in the first 10 h and then increased 18.5% at 24 h, whereas the liver fru-1,8-P(2)ase mRNA increased ca. 20 % during the first, 10 h and then up to 161.1 +/- 18.0% at 24 h compar ed to that at 100.0 +/- 11.4% (0 h); (iv) euglycemic hyperinsulinemia did not change the renal fru-1,6-P(2)ase mRNA level, but lowered the h epatic fru-1,6-P(2)ase mRNA level to 56.0 +/- 8.7 from 100.0 +/- 11.8% (fasted controls) in newborn dogs, which was identical to that in adu lt dogs. These data suggest that the fru-1,6-P(2)ase in liver may play a more important role in glucose homeostasis of newborn dogs than tha t in kidney during the first day of their lives and that the incomplet e suppression of transcription of the hepatic fru-1,6-P(2)ase gene by insulin in newborn dogs may mot contribute to neonatal hyperglycemia d ue to insulin resistance. (C) 1997 Academic Press.