Use of 2H2O for estimating rates of gluconeogenesis: Determination and correction of error due to transaldolase exchange

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Abstract

The use of deuterated water as a method to measure gluconeogenesis has previously been well validated and is reflective of normal human physiology. However, there has been concern since the method was first introduced that transaldolase exchange may lead to the overestimation of gluconeogenesis. We examined the impact of transaldolase exchange on the estimation of gluconenogenesis using the deuterated water method under a variety of physiological conditions in humans by using the gluconeogenic tracer [U-13C]propionate, 2H2O, and 2H/13C nuclear magnetic resonance (NMR) spectroscopy. When [U-13C]propionate was used, 13C labeling inequality occurred between the top and bottom halves of glucose in individuals fasted for 12-24 h who were weight stable (n = 18) or had lost weight via calorie restriction (n = 7), consistent with transaldolase exchange. Similar analysis of glucose standards revealed no significant difference in the total 13C enrichment between the top and bottom halves of glucose, indicating that the differences detected were biological, not analytical, in origin. This labeling inequality was attenuated by extending the fasting period to 48 h (n = 12) as well as by dietary carbohydrate restriction (n = 7), both conditions associated with decreased glycogenolysis. These findings were consistent with a transaldolase effect; however, the resultant overestimation of gluconeogenesis in the overnight-fasted state was modest (7-12%), leading to an error of 14-24% that was easily correctable by using either a simultaneous 13C gluconeogenic tracer or a correction nomogram generated from data in the present study.

Original languageEnglish (US)
Pages (from-to)E1304-E1312
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume303
Issue number11
DOIs
StatePublished - Dec 1 2012

Keywords

  • Deuterated water
  • Gluconeogenesis
  • Glycogenolysis
  • Stable isotope
  • Transaldolase

ASJC Scopus subject areas

  • General Medicine

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