A dual-isotope technique for determination of in vivo ketone body kinetics

J. M. Miles, W. F. Schwenk, K. L. McClean, M. W. Haymond

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

'Total ketone body specific activity' has been widely used in studies of ketone body metabolism to circumvent so-called 'isotope disequilibrium' between the two major ketone body pools, acetoacetate and β-hydroxybutyrate. Recently, this approach has been criticized on theoretical grounds. In the present studies, [13C]acetoacetate and β-[14C]hydroxybutyrate were simultaneously infused in nine mongrel dogs before and during an infusion of either unlabeled sodium acetoacetate or unlabeled sodium β-hydroxybutyrate. Ketone body turnover was determined using total ketone body specific activity, total ketone body moles % enrichment, and an open two-pool model, both before and during the exogenous infusion of unlabeled ketone bodies. Basal ketone body turnover rates were significantly higher using [13C]acetoacetate than with either β-[14C]hydroxybutyrate alone or the dual-isotope model (3.6 ± 0.5 vs. 2.2 ± 0.2 and 2.7 ± 0.2 μmol·kg-1·min-1, respectively, P < 0.05). During exogenous infusion of unlabeled sodium acetoacetate, the dual-isotope model provided the best estimate of ketone body inflow, whereas 14C specific activity underestimated the known rate of acetoacetate infusion by 55% (P < 0.02). During sodium β-hydroxybutyrate infusion, [13C]-acetoacetate overestimated ketone body inflow by 55% (P = NS), while better results were obtained with 14C β-hydroxybutyrate alone and the two-pool model. Ketone body interconversion as estimated by the dual-isotope technique increased markedly during exogenous ketone body infusion. In conclusion, significant errors in estimation of ketone body inflow were made using single-isotope techniques, whereas a dual-isotope model provided reasonably accurate estimates of ketone body inflow during infusion of exogenous acetoacetate and β-hydroxybutyrate. In addition, the dual-isotope technique can provide estimates of ketone body interconversion. The dual-isotope model may offer significant advantages over single-isotope methods for studying ketone body metabolism in vivo.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume251
Issue number2
StatePublished - 1986

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Ketone Bodies
Isotopes
Kinetics
Hydroxybutyrates
Sodium
Metabolism
acetoacetic acid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology

Cite this

A dual-isotope technique for determination of in vivo ketone body kinetics. / Miles, J. M.; Schwenk, W. F.; McClean, K. L.; Haymond, M. W.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 251, No. 2, 1986.

Research output: Contribution to journalArticle

Miles, J. M. ; Schwenk, W. F. ; McClean, K. L. ; Haymond, M. W. / A dual-isotope technique for determination of in vivo ketone body kinetics. In: American Journal of Physiology - Endocrinology and Metabolism. 1986 ; Vol. 251, No. 2.
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abstract = "'Total ketone body specific activity' has been widely used in studies of ketone body metabolism to circumvent so-called 'isotope disequilibrium' between the two major ketone body pools, acetoacetate and β-hydroxybutyrate. Recently, this approach has been criticized on theoretical grounds. In the present studies, [13C]acetoacetate and β-[14C]hydroxybutyrate were simultaneously infused in nine mongrel dogs before and during an infusion of either unlabeled sodium acetoacetate or unlabeled sodium β-hydroxybutyrate. Ketone body turnover was determined using total ketone body specific activity, total ketone body moles {\%} enrichment, and an open two-pool model, both before and during the exogenous infusion of unlabeled ketone bodies. Basal ketone body turnover rates were significantly higher using [13C]acetoacetate than with either β-[14C]hydroxybutyrate alone or the dual-isotope model (3.6 ± 0.5 vs. 2.2 ± 0.2 and 2.7 ± 0.2 μmol·kg-1·min-1, respectively, P < 0.05). During exogenous infusion of unlabeled sodium acetoacetate, the dual-isotope model provided the best estimate of ketone body inflow, whereas 14C specific activity underestimated the known rate of acetoacetate infusion by 55{\%} (P < 0.02). During sodium β-hydroxybutyrate infusion, [13C]-acetoacetate overestimated ketone body inflow by 55{\%} (P = NS), while better results were obtained with 14C β-hydroxybutyrate alone and the two-pool model. Ketone body interconversion as estimated by the dual-isotope technique increased markedly during exogenous ketone body infusion. In conclusion, significant errors in estimation of ketone body inflow were made using single-isotope techniques, whereas a dual-isotope model provided reasonably accurate estimates of ketone body inflow during infusion of exogenous acetoacetate and β-hydroxybutyrate. In addition, the dual-isotope technique can provide estimates of ketone body interconversion. The dual-isotope model may offer significant advantages over single-isotope methods for studying ketone body metabolism in vivo.",
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