Developmental Aspects of Transcription of Fructose- 1,6-Bisphosphatase in Newborn Dogs

Abstract

Our previous investigations demonstrated that unsuppressed gluconeogenesis under hyperinsulinemia in newborn dogs may be a mechanism of neonatal hyperglycemia. In the present study, the transcription of the gene for fructose-1,6-bisphosphatase (fru-1,6-P₂ase; E 3.1.3.11) of newborn dogs was studied under various metabolic perturbations (age, suckling, fasting, and hyperinsulinemia). Total RNAs isolated from livers and kidneys were hybridized with a rat fru-1,6-P₂ase cDNA probe. We observed that (i) fru-1,6-P₂ase mRNA was expressed in both kidney and liver at birth and was about 40 and 80% of those in kidney and liver of adult dog, respectively; (ii) suckling decreased the kidney fru-1,6-P₂ase 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-1,6-P₂ase mRNA level did not change in the first 10 h and then increased 18.5% at 24 h, whereas the liver fru-1,6-P₂ase mRNA increased ca. 20% during the first 10 h and then up to 161.1 ± 18.0% at 24 h compared to that at 100.0 ± 11.4% (0 h); (iv) euglycemic hyperinsulinemia did not change the renal fru-1,6-P₂ase mRNA level, but lowered the hepatic fru-1,6-P₂ase mRNA level to 56.0 ± 8.7 from 100.0 ± 11.8% (fasted controls) in newborn dogs, which was identical to that in adult dogs. These data suggest that the fru-1,6-P₂ase in liver may play a more important role in glucose homeostasis of newborn dogs than that in kidney during the first day of their lives and that the incomplete suppression of transcription of the hepatic fru-1,6-P₂ase gene by insulin in newborn dogs may not contribute to neonatal hyperglycemia due to insulin resistance.