Document Detail


Transaldolase exchange and its effects on measurements of gluconeogenesis in humans.
MedLine Citation:
PMID:  21062960     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The deuterated water method is used extensively to measure gluconeogenesis in humans. This method assumes negligible exchange of the lower three carbons of fructose 6-phsophate via transaldolase exchange since this exchange will result in enrichment of carbon 5 of glucose in the absence of net gluconeogenesis. The present studies tested this assumption. ²H₂O and acetaminophen were ingested and [1-¹³C]acetate infused in 11 nondiabetic subjects after a 16-h fast. Plasma and urinary glucuronide enrichments were measured using nuclear magnetic resonance spectroscopy before and during a 0.35 mU·kg FFM⁻¹·min⁻¹ insulin infusion. Rates of endogenous glucose production measured with [3-³H]- and [6,6-²H₂]glucose did not differ either before (14.0 ± 0.7 vs. 13.8 ± 0.7 μmol·kg⁻¹·min⁻¹) or during the clamp (10.4 ± 0.9 vs. 10.9 ± 0.7 μmol·kg⁻¹·min⁻¹), consistent with equilibration and quantitative removal of tritium during triose isomerase exchange. Plasma [3-¹³C] glucose-to-[4-¹³C]glucose and urinary [3-¹³C] glucuronide-to-[4-¹³C]glucuronide ratios were <1.0 (P < 0.001) in all subjects both before (0.66 ± 0.04 and 0.60 ± 0.04) and during (059 ± 0.05 and 0.56 ± 0.06) the insulin infusion, respectively, indicating that ∼35-45% of the labeling of the 5th carbon of glucose by deuterium was due to transaldolase exchange rather than gluconeogenesis. When corrected for transaldolase exchange, rates of gluconeogenesis were lower (P < 0.001) and glycogenolysis higher (P < 0.001) than uncorrected rates both before and during the insulin infusion. In conclusion, assuming negligible dilution by glycerol and near-complete triose isomerase equilibration, these data provide strong experimental evidence that transaldolase exchange occurs in humans, resulting in an overestimate of gluconeogenesis and an underestimate of glycogenolysis when measured with the ²H₂O method. Use of appropriate ¹³C tracers provides a means of correcting for transaldolase exchange.
Authors:
Rita Basu; Cristina Barosa; Ananda Basu; Vishwanath Pattan; Ahmed Saad; John Jones; Robert Rizza
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-11-09
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  300     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-28     Completed Date:  2011-03-03     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  E296-303     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetates / metabolism
Adult
Blood Glucose / metabolism
C-Peptide / metabolism
Carbon Radioisotopes / diagnostic use
Deuterium Oxide / diagnostic use
Female
Glucagon / metabolism
Gluconeogenesis / physiology*
Glucose / metabolism
Glyceraldehyde 3-Phosphate / metabolism
Humans
Insulin / blood
Isotope Labeling
Magnetic Resonance Spectroscopy
Male
Middle Aged
Transaldolase / metabolism*
Grant Support
ID/Acronym/Agency:
1-UL1-RR-024150/RR/NCRR NIH HHS; DK-29953/DK/NIDDK NIH HHS; R01 DK029953/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Acetates; 0/Blood Glucose; 0/C-Peptide; 0/Carbon Radioisotopes; 0/Insulin; 142-10-9/Glyceraldehyde 3-Phosphate; 9007-92-5/Glucagon; EC 2.2.1.2/Transaldolase; IY9XDZ35W2/Glucose; J65BV539M3/Deuterium Oxide
Comments/Corrections

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