Mechanism for underestimation of isotopically determined glucose disposal
Use of (3H)glucose and a one-compartment model to determine glucose kinetics frequently underestimates the rate of glucose production (Ra). To assess to what extent an isotope effect, a tracer contaminant, or inadequacy of the model was responsible, we measured glucose Ra and forearm clearance of tracer and unlabeled glucose at various concentrations of plasma insulin (approximately 50, approximately 160, and approximately 1800 microU/ml) and plasma glucose (approximately 90, approximately 160, approximately 250, and approximately 400 mg/dl) under steady-state and non-steady-state conditions. Under isotopic steady-state conditions, the clearances of tracer and unlabeled glucose across the forearm were identical, and exogenous glucose infusion rates did not differ significantly from the isotopically determined glucose Ra (10.0 +/- 1.3 vs. 10.5 +/- 1.0 mg.kg-1 fat-free mass.min-1, respectively). However, under isotopic non-steady-state conditions, the isotopically determined Ra was significantly lower than the glucose infusion rate (11.5 +/- 1.3 vs. 13.7 +/- 1.5 mg.kg-1 fat-free mass.min-1, respectively, P less than .001), and the underestimation was related to the deviation from the isotopic steady state. When (3H)glucose specific activity of plasma samples from experiments with the greatest underestimation of Ra was determined by high-performance liquid chromatography, less than 7% of the underestimation could be accounted for by a contaminant. These results indicate that inadequacy of the one-compartment model is responsible for underestimation of glucose Ra under non-steady-state conditions and that there is no detectable isotopic effect or appreciable contaminant of (3-3H)glucose. We conclude that under isotopic steady-state conditions, (3-3H)glucose is a reliable tracer for glucose kinetic studies in humans.
- Research Organization:
- National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ (USA)
- OSTI ID:
- 5933913
- Journal Information:
- Diabetes; (United States), Journal Name: Diabetes; (United States) Vol. 38:6; ISSN DIAEA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
ANIMALS
CARBOHYDRATES
CHROMATOGRAPHY
GLUCOSE
HEXOSES
HORMONES
INSULIN
ISOTOPE APPLICATIONS
ISOTOPE DILUTION
ISOTOPE EFFECTS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MAN
METABOLISM
MONOSACCHARIDES
ORGANIC COMPOUNDS
PEPTIDE HORMONES
PRIMATES
SACCHARIDES
SEPARATION PROCESSES
STEADY-STATE CONDITIONS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES