Measurement of hepatic glucose output, krebs cycle, and gluconeogenic fluxes by NMR analysis of a single plasma glucose sample

John G. Jones, Rui A. Carvalho, Byron Franco, A. Dean Sherry, Craig R. Malloy

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Abstract

13C and 1H NMR spectroscopy of plasma glucose was used to resolve the isotopomer contributions from tracer levels of [1,6-13C2]glucose, a novel tracer of glucose carbon skeleton turnover, and [U-13C]propionate, a tracer of hepatic citric acid cycle metabolism. This allowed simultaneous measurements of hepatic glucose production and citric acid cycle fluxes from the MR analysis of a single plasma glucose sample in fasted animals. Glucose carbon skeleton turnover, as reported by the dilution of [1,6- 13C2]glucose, was 56 ± 2 μmol/kg/min in the presence of labeling from [U-13C]propionate and 53 ± 4 μmol/kg/min in its absence. Therefore, as expected, the labeling contributions from [U-13C]propionate metabolism did not have a significant effect on the measurement of glucose turnover. For the group infused with both tracers, citric acid cycle flux estimates from the analysis of glucose C2 isotopomer ratios were consistent with those from our recent experiments where only [U-13C]propionate was infused, verifying that the presence of [1,6-13C2]glucose did not interfere with these measurements. This integrated analysis of hepatic glucose output and citric acid cycle fluxes from plasma glucose isotopomers yielded a noninvasive estimate of hepatic citrate synthase flux of 74 ± 12 μmol/kg/min for 24-h fasted rats.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalAnalytical Biochemistry
Volume263
Issue number1
DOIs
StatePublished - Oct 1 1998

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Citric Acid Cycle
Nuclear magnetic resonance
Fluxes
Plasmas
Glucose
Liver
Propionates
Metabolism
Skeleton
Labeling
Carbon
Citrate (si)-Synthase
Nuclear magnetic resonance spectroscopy
Dilution
Rats
Animals
Magnetic Resonance Spectroscopy

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Measurement of hepatic glucose output, krebs cycle, and gluconeogenic fluxes by NMR analysis of a single plasma glucose sample. / Jones, John G.; Carvalho, Rui A.; Franco, Byron; Sherry, A. Dean; Malloy, Craig R.

In: Analytical Biochemistry, Vol. 263, No. 1, 01.10.1998, p. 39-45.

Research output: Contribution to journalArticle

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AB - 13C and 1H NMR spectroscopy of plasma glucose was used to resolve the isotopomer contributions from tracer levels of [1,6-13C2]glucose, a novel tracer of glucose carbon skeleton turnover, and [U-13C]propionate, a tracer of hepatic citric acid cycle metabolism. This allowed simultaneous measurements of hepatic glucose production and citric acid cycle fluxes from the MR analysis of a single plasma glucose sample in fasted animals. Glucose carbon skeleton turnover, as reported by the dilution of [1,6- 13C2]glucose, was 56 ± 2 μmol/kg/min in the presence of labeling from [U-13C]propionate and 53 ± 4 μmol/kg/min in its absence. Therefore, as expected, the labeling contributions from [U-13C]propionate metabolism did not have a significant effect on the measurement of glucose turnover. For the group infused with both tracers, citric acid cycle flux estimates from the analysis of glucose C2 isotopomer ratios were consistent with those from our recent experiments where only [U-13C]propionate was infused, verifying that the presence of [1,6-13C2]glucose did not interfere with these measurements. This integrated analysis of hepatic glucose output and citric acid cycle fluxes from plasma glucose isotopomers yielded a noninvasive estimate of hepatic citrate synthase flux of 74 ± 12 μmol/kg/min for 24-h fasted rats.

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