title: 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.
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.
  
  
  METHODS
  Six nondiabetic subjects were infused with [3,5-(2)H(2)]glucose and insulin while glucose was clamped at approximately 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 (2)H(2)O, 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).
authors.affiliation: Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
authors.forename: Gerlies
authors.initials: G
authors.lastname: Bock
authors.forename: William C
authors.initials: WC
authors.lastname: Schumann
authors.forename: Rita
authors.initials: R
authors.lastname: Basu
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Burgess
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yan
authors.forename: Visvanathan
authors.initials: V
authors.lastname: Chandramouli
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Landau
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood*; D017666:Deuterium Oxide / Q000378:metabolism*; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000737:chemistry* / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D007328:Insulin / Q000097:blood* / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014316:Tritium
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D014316:Tritium; D005947:Glucose; D017666:Deuterium Oxide