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 ~2H_2O to Measure Gluconeogenesis in Humans

摘要

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-~2H_2]glucose and insulin while glucose was clamped at ～ 5 mmol/1; 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 triosephos-phate isomerase due to a kinetic isotope effect. After ingestion of ~2H_2O, 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).