Evidence that processes other than gluconeogenesis may influence the ratio of deuterium on the fifth and third carbons of glucose: Implications for the use of 2H2O to measure gluconeogenesis in humans

Gerlies Bock, William C. Schumann, Rita Basu, Shawn C. Burgess, Zheng Yan, Visvanathan Chandramouli, Robert A. Rizza, Bernard R. Landau

Research output: Contribution to journalArticle

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Abstract

OBJECTIVE - The deuterated water method uses the ratio of deuterium on carbons 5 and 2 (C5/C2) or 3 and 2 (C3/C2) to estimate the fraction of glucose derived from gluconeogenesis. The current studies determined whether C3 and C5 glucose enrichment is influenced by processes other than gluconeogenesis. RESEARCH DESIGN AND METHODS - Six nondiabetic subjects were infused with [3,5-2H2]glucose and insulin while glucose was clamped at ∼5 mmol/l; the C5-to-C3 ratio was measured in the in UDP-glucose pool using nuclear magnetic resonance and the acetaminophen glucuronide method. RESULTS - Whereas the C5-to-C3 ratio of the infusate was 1.07, the ratio in UDP-glucose was <1.0 in all subjects both before (0.75 ± 0.07) and during (0.67 ± 0.05) the insulin infusion. CONCLUSIONS - These data indicate that the deuterium on C5 of glucose is lost more rapidly relative to the deuterium on C3. The decrease in the C5-to-C3 ratio could result from exchange of the lower three carbons of fructose-6-phosphate with unlabeled three-carbon precursors via the transaldolase reaction and/or selective retention of the C3 deuterium at the level of triosephosphate isomerase due to a kinetic isotope effect. After ingestion of 2H2O, these processes would increase the enrichment of C5 and decrease the enrichment of C3, respectively, with the former causing an overestimation of gluconeogenesis using the C2-to-C5 ratio and the latter an underestimation using the C3-to-C2 ratio. Future studies will be required to determine whether the impact of these processes on the measurement of gluconeogenesis differs among the disease states being evaluated (e.g., diabetes or obesity).

Original languageEnglish (US)
Pages (from-to)50-55
Number of pages6
JournalDiabetes
Volume57
Issue number1
DOIs
StatePublished - Jan 2008

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Gluconeogenesis
Deuterium
Carbon
Glucose
Uridine Diphosphate Glucose
Transaldolase
Triose-Phosphate Isomerase
Insulin
Isotopes
Research Design
Magnetic Resonance Spectroscopy
Obesity
Eating
Water

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Evidence that processes other than gluconeogenesis may influence the ratio of deuterium on the fifth and third carbons of glucose : Implications for the use of 2H2O to measure gluconeogenesis in humans. / Bock, Gerlies; Schumann, William C.; Basu, Rita; Burgess, Shawn C.; Yan, Zheng; Chandramouli, Visvanathan; Rizza, Robert A.; Landau, Bernard R.

In: Diabetes, Vol. 57, No. 1, 01.2008, p. 50-55.

Research output: Contribution to journalArticle

Bock, Gerlies ; Schumann, William C. ; Basu, Rita ; Burgess, Shawn C. ; Yan, Zheng ; Chandramouli, Visvanathan ; Rizza, Robert A. ; Landau, Bernard R. / Evidence that processes other than gluconeogenesis may influence the ratio of deuterium on the fifth and third carbons of glucose : Implications for the use of 2H2O to measure gluconeogenesis in humans. In: Diabetes. 2008 ; Vol. 57, No. 1. pp. 50-55.
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abstract = "OBJECTIVE - The deuterated water method uses the ratio of deuterium on carbons 5 and 2 (C5/C2) or 3 and 2 (C3/C2) to estimate the fraction of glucose derived from gluconeogenesis. The current studies determined whether C3 and C5 glucose enrichment is influenced by processes other than gluconeogenesis. RESEARCH DESIGN AND METHODS - Six nondiabetic subjects were infused with [3,5-2H2]glucose and insulin while glucose was clamped at ∼5 mmol/l; the C5-to-C3 ratio was measured in the in UDP-glucose pool using nuclear magnetic resonance and the acetaminophen glucuronide method. RESULTS - Whereas the C5-to-C3 ratio of the infusate was 1.07, the ratio in UDP-glucose was <1.0 in all subjects both before (0.75 ± 0.07) and during (0.67 ± 0.05) the insulin infusion. CONCLUSIONS - These data indicate that the deuterium on C5 of glucose is lost more rapidly relative to the deuterium on C3. The decrease in the C5-to-C3 ratio could result from exchange of the lower three carbons of fructose-6-phosphate with unlabeled three-carbon precursors via the transaldolase reaction and/or selective retention of the C3 deuterium at the level of triosephosphate isomerase due to a kinetic isotope effect. After ingestion of 2H2O, these processes would increase the enrichment of C5 and decrease the enrichment of C3, respectively, with the former causing an overestimation of gluconeogenesis using the C2-to-C5 ratio and the latter an underestimation using the C3-to-C2 ratio. Future studies will be required to determine whether the impact of these processes on the measurement of gluconeogenesis differs among the disease states being evaluated (e.g., diabetes or obesity).",
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T1 - Evidence that processes other than gluconeogenesis may influence the ratio of deuterium on the fifth and third carbons of glucose

T2 - Implications for the use of 2H2O to measure gluconeogenesis in humans

AU - Bock, Gerlies

AU - Schumann, William C.

AU - Basu, Rita

AU - Burgess, Shawn C.

AU - Yan, Zheng

AU - Chandramouli, Visvanathan

AU - Rizza, Robert A.

AU - Landau, Bernard R.

PY - 2008/1

Y1 - 2008/1

N2 - OBJECTIVE - The deuterated water method uses the ratio of deuterium on carbons 5 and 2 (C5/C2) or 3 and 2 (C3/C2) to estimate the fraction of glucose derived from gluconeogenesis. The current studies determined whether C3 and C5 glucose enrichment is influenced by processes other than gluconeogenesis. RESEARCH DESIGN AND METHODS - Six nondiabetic subjects were infused with [3,5-2H2]glucose and insulin while glucose was clamped at ∼5 mmol/l; the C5-to-C3 ratio was measured in the in UDP-glucose pool using nuclear magnetic resonance and the acetaminophen glucuronide method. RESULTS - Whereas the C5-to-C3 ratio of the infusate was 1.07, the ratio in UDP-glucose was <1.0 in all subjects both before (0.75 ± 0.07) and during (0.67 ± 0.05) the insulin infusion. CONCLUSIONS - These data indicate that the deuterium on C5 of glucose is lost more rapidly relative to the deuterium on C3. The decrease in the C5-to-C3 ratio could result from exchange of the lower three carbons of fructose-6-phosphate with unlabeled three-carbon precursors via the transaldolase reaction and/or selective retention of the C3 deuterium at the level of triosephosphate isomerase due to a kinetic isotope effect. After ingestion of 2H2O, these processes would increase the enrichment of C5 and decrease the enrichment of C3, respectively, with the former causing an overestimation of gluconeogenesis using the C2-to-C5 ratio and the latter an underestimation using the C3-to-C2 ratio. Future studies will be required to determine whether the impact of these processes on the measurement of gluconeogenesis differs among the disease states being evaluated (e.g., diabetes or obesity).

AB - OBJECTIVE - The deuterated water method uses the ratio of deuterium on carbons 5 and 2 (C5/C2) or 3 and 2 (C3/C2) to estimate the fraction of glucose derived from gluconeogenesis. The current studies determined whether C3 and C5 glucose enrichment is influenced by processes other than gluconeogenesis. RESEARCH DESIGN AND METHODS - Six nondiabetic subjects were infused with [3,5-2H2]glucose and insulin while glucose was clamped at ∼5 mmol/l; the C5-to-C3 ratio was measured in the in UDP-glucose pool using nuclear magnetic resonance and the acetaminophen glucuronide method. RESULTS - Whereas the C5-to-C3 ratio of the infusate was 1.07, the ratio in UDP-glucose was <1.0 in all subjects both before (0.75 ± 0.07) and during (0.67 ± 0.05) the insulin infusion. CONCLUSIONS - These data indicate that the deuterium on C5 of glucose is lost more rapidly relative to the deuterium on C3. The decrease in the C5-to-C3 ratio could result from exchange of the lower three carbons of fructose-6-phosphate with unlabeled three-carbon precursors via the transaldolase reaction and/or selective retention of the C3 deuterium at the level of triosephosphate isomerase due to a kinetic isotope effect. After ingestion of 2H2O, these processes would increase the enrichment of C5 and decrease the enrichment of C3, respectively, with the former causing an overestimation of gluconeogenesis using the C2-to-C5 ratio and the latter an underestimation using the C3-to-C2 ratio. Future studies will be required to determine whether the impact of these processes on the measurement of gluconeogenesis differs among the disease states being evaluated (e.g., diabetes or obesity).

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