Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps

Journal Article · Mon Aug 01 04:00:00 EDT 1988 · Diabetes; (United States)

DOI:https://doi.org/10.2337/diab.37.8.1025· OSTI ID:7188308

Finegood, D T; Bergman, R N; Vranic, M

We previously demonstrated that conventional tracer methods applied to euglycemic-hyperinsulinemic glucose clamps result in substantially negative estimates for the rate of endogenous glucose production, particularly during the first half of 180-min clamps. We also showed that addition of tracer to the exogenous glucose infusate resulted in nonnegative endogenous glucose production (Ra) estimates. In this study, we investigated the underlying cause of negative estimates of Ra from conventional clamp/tracer methods and the reason for the difference in estimates when tracer is added to the exogenous glucose infusate. We performed euglycemic-hyperinsulinemic (300-microU/ml) clamps in normal dogs without (cold GINF protocol, n = 6) or with (hot GINF protocol, n = 6) tracer (D-(3-3H)glucose) added to the exogenous glucose infusate. In the hot GINF protocol, sufficient tracer was added to the exogenous glucose infusate such that arterial plasma specific activity (SAa) did not change from basal through the clamp period (P greater than .05). In the cold GINF studies, plasma SAa fell 81 +/- 2% from the basal level by the 3rd h of clamping. We observed a significant, transient, positive venous-arterial difference in specific activity (SAv-SAa difference) during the cold GINF studies. The SAv-SAa difference reached a peak of 27 +/- 6% at 30 min and diminished to a plateau of 7 +/- 1% between 70 and 180 min. We also observed a positive but constant SAv-SAa difference (4.6 +/- 0.2% between 10 and 180 min) during the hot GINF studies.

• Research Organization: Univ. of Toronto, Ontario (Canada)
• OSTI ID: 7188308
• Journal Information: Diabetes; (United States), Journal Name: Diabetes; (United States) Vol. 37:8; ISSN DIAEA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALDEHYDES
ANIMALS
BIOSYNTHESIS
CARBOHYDRATES
DOGS
ERRORS
GLUCOSE
HEXOSES
HORMONES
IMMUNOASSAY
IMMUNOLOGY
INSULIN
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MONOSACCHARIDES
ORGANIC COMPOUNDS
PEPTIDE HORMONES
RADIOASSAY
RADIOIMMUNOASSAY
RADIOIMMUNOLOGY
SACCHARIDES
SYNTHESIS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VASOCONSTRICTION
VERTEBRATES