Gluconeogenesis and the protection of hepatic intracellular pH during diabetic ketoacidosis in rats.
Studies were made of the mechanism whereby hepatic gluconeogenesis is increased in diabetic ketoacidosis (DKA) despite evidence in vitro of inhibition of gluconeogenesis by systemic acidosis. In perfused livers taken from normal rats, marked inhibition of lactate uptake and glucose output was achieved by simulation of metabolic acidosis in the perfusate. In perfused livers obtained from animals with DKA, lactate uptake and glucose output were greater than in normal perfused liver at all values of perfusate pH, and it was not possible to demonstrate significant inhibition of gluconeogenesis from lactate by perfusate acidosis. Varying severity of acidosis was induced in rats by (a) HCl infusion, (b) NH4Cl ingestion or (c) experimental DKA. Hepatic intracellular pH (pHi) was measured in vivo by 31P-n.m.r. spectroscopy. Whereas at the severer degrees of systemic acidosis marked falls in hepatic pHi were seen in the HCl- and NH4Cl-treated animals, little fall was seen in rats with DKA. The protection of hepatic pHi in rats with DKA was not due to differences in respiratory compensation compared with the other groups. It is suggested that this protection of hepatic pHi in DKA may be responsible for the failure of acidotic inhibition of gluconeogenesis from lactate. Possible reasons for pHi protection in DKA are considered. There is no difference in hepatic energy status as assessed in vivo by ATP/Pi ratios between control, DKA and NH4Cl-treated rats. DKA rats show a striking decrease in hepatic glycerophosphoethanolamine content.
Beech
J S
JS
Medical Unit, London Hospital Medical College University of London, UK.
Williams
S R
SR
Cohen
R D
RD
Iles
R A
RA
D020155:3-Hydroxybutyric Acid; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D016883:Diabetic Ketoacidosis / Q000378:metabolism*; D004734:Energy Metabolism; D005943:Gluconeogenesis; D006863:Hydrogen-Ion Concentration; D006885:Hydroxybutyrates / Q000494:pharmacology; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009132:Muscles / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010714:Phosphatidylethanolamines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000227:Adenine Nucleotides; D006885:Hydroxybutyrates; D007773:Lactates; D010710:Phosphates; D010714:Phosphatidylethanolamines; C002449:glycerophosphoethanolamine; D002245:Carbon Dioxide; D020155:3-Hydroxybutyric Acid