title: Systemic pH modifies ketone body production rates and lipolysis in humans.
abstract: To investigate whether changes in systemic pH influence ketone body production or utilization, total ketone body (TK) kinetics were measured with [3-14C]acetoacetate and D-beta-[1,3-13C2]hydroxybutyrate tracers in overnight fasted subjects during metabolic alkalosis (NaHCO3 infusion) or acidosis [NH4Cl ingestion or arginine (Arg)-HCl infusion]. Somatostatin, with insulin, glucagon, and growth hormone replacement, was infused in all studies. Blood pH and HCO3- (mM) increased from baseline (0-30 min) to 180-210 min by 0.08 +/- 0.02 and 7 +/- 1 with NaHCO3 and decreased by 0.08 +/- 0.2 and 7 +/- 1 or 5 +/- 1 with NH4Cl or Arg-HCl (all P less than 0.005). Over this period blood TK (microM) differed between the NaHCO3 (+198 +/- 65) and both NH4Cl (-90 +/- 53) and Arg-HCl (-154 +/- 55) (P less than 0.05). These changes resulted from parallel alterations in TK production rate of appearance (Ra TK, mumol.kg-1.min-1), because changes from baseline in Ra 14C TK also differed between NaHCO3 (+1.9 +/- 0.8) and NH4Cl (-1.0 +/- 0.6) and Arg-HCl (-2.0 +/- 0.5) (P less than 0.05). Ra TK calculated with single- or dual-tracer techniques were similar. Blood free fatty acids (FFA) increased with NaHCO3, and FFA and glycerol decreased with NH4Cl and Arg-HCl, suggesting that FFA availability mediated the pH effects on hepatic ketogenesis. These results demonstrate that modest changes in systemic pH modify FFA availability and TK production rates.
authors.affiliation: College of Medicine, University of Vermont, Burlington 05405.
authors.forename: V L
authors.initials: VL
authors.lastname: Hood
authors.forename: U
authors.initials: U
authors.lastname: Keller
authors.forename: M W
authors.initials: MW
authors.lastname: Haymond
authors.forename: D
authors.initials: D
authors.lastname: Küry
mesh_terms: D000136:Acid-Base Equilibrium; D000328:Adult; D000643:Ammonium Chloride / Q000494:pharmacology; D001120:Arginine / Q000494:pharmacology; D001639:Bicarbonates / Q000097:blood / Q000494:pharmacology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007657:Ketone Bodies / Q000097:blood / Q000378:metabolism*; D008066:Lipolysis; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012964:Sodium / Q000494:pharmacology; D017693:Sodium Bicarbonate; D013004:Somatostatin / Q000494:pharmacology
chemical_list: D001639:Bicarbonates; D007328:Insulin; D007657:Ketone Bodies; D000643:Ammonium Chloride; D013004:Somatostatin; D017693:Sodium Bicarbonate; D001120:Arginine; D012964:Sodium