Determination of the 13C-Labeling Pattern of Glucose by Gas Chromatography-Mass Spectrometry

Beylot, M.; Previs, Stephen F.; David, F.; Brunengraber, Henri

doi:10.1006/abio.1993.1363

Cited by 66 publications

(69 citation statements)

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“…Glucose concentrations were measured using a glucose oxidase method (Yellow Springs Instrument, Yellow Springs, OH). Plasma [6,6-2 H 2 ]glucose and [1-13 C]glucose enrichments were measured using gas chromatographic mass spectrometry (Thermoquest, San Jose, CA) to simultaneously monitor the C-1 and C-2 as well as C-3 to C-6 fragments, as described by Beylot et al (9), and [6-3 H]glucose specific activity by liquid scintillation counting (supplemental appendix). Calculation of glucose appearance and disappearance rates.…”

Section: Methodsmentioning

confidence: 99%

Effects of Dipeptidyl Peptidase-4 Inhibition on Gastrointestinal Function, Meal Appearance, and Glucose Metabolism in Type 2 Diabetes

et al. 2007

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OBJECTIVE-We sought to determine whether alterations in meal absorption and gastric emptying contribute to the mechanism by which inhibitors of dipeptidyl peptidase-4 (DPP-4) lower postprandial glucose concentrations.RESEARCH DESIGN AND METHODS-We simultaneously measured gastric emptying, meal appearance, endogenous glucose production, and glucose disappearance in 14 subjects with type 2 diabetes treated with either vildaglipitin (50 mg b.i.d.) or placebo for 10 days using a double-blind, placebo-controlled, randomized, crossover design.RESULTS-Fasting (7.3 Ϯ 0.5 vs. 7.9 Ϯ 0.5 mmol/l) and peak postprandial (14.1 Ϯ 0.6 vs. 15.9 Ϯ 0.9 mmol/l) glucose concentrations were lower (P Ͻ 0.01) after vildagliptin treatment than placebo. Despite lower glucose concentrations, postprandial insulin and C-peptide concentrations did not differ during the two treatments. On the other hand, the integrated (area under the curve) postprandial glucagon concentrations were lower (20.9 Ϯ 1.6 vs. 23.7 Ϯ 1.3 mg/ml per 5 h, P Ͻ 0.05), and glucagon-like peptide 1 (GLP-1) concentrations were higher (1,878 Ϯ 270 vs. 1,277 Ϯ 312 pmol/l per 5 h, P ϭ 0.001) during vildagliptin administration compared with placebo. Gastric emptying and meal appearance did not differ between treatments.CONCLUSIONS-Vildagliptin does not alter gastric emptying or the rate of entry of ingested glucose into the systemic circulation in humans. DPP-4 inhibitors do not lower postprandial glucose concentrations by altering the rate of nutrient absorption or delivery to systemic circulation. Alterations in islet function, secondary to increased circulating concentrations of active GLP-1, are associated with the decreased postprandial glycemic excursion observed in the presence of vildagliptin.

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Section: Methodsmentioning

confidence: 99%

Effects of Dipeptidyl Peptidase-4 Inhibition on Gastrointestinal Function, Meal Appearance, and Glucose Metabolism in Type 2 Diabetes

et al. 2007

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“…Enrichments were calculated from the ratio of [U- 13 C]glucose/[ 12 C]glucose during the last 30 min of the basal period and during the last 60 min of the clamp (i.e., steady-state conditions). This ratio was determined by gas chromatography-mass spectrometry (GC-MS) analyses of derivatized glucose from blood samples following literature protocols (29,30).…”

Section: Methodsmentioning

confidence: 99%

Muscle-Type Specific Intramyocellular and Hepatic Lipid Metabolism During Starvation in Wistar Rats

Neumann-Haefelin

Beha²,

Kuhlmann³

et al. 2004

Diabetes

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“…Calculations-The mass isotopomer distribution of glucose was determined on the permethyl and aldonitrile pentaacetate derivatives of glucose (11,23). The measured MID was corrected for natural enrichment at each mass (11,18) by a technique that takes into account the skew of natural 13 C enrichment of molecules as increasing numbers of carbon atoms become fully labeled (24).…”

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Limitations of the Mass Isotopomer Distribution Analysis of Glucose to Study Gluconeogenesis

Previs

Hallowell

Neimanis

et al. 1998

Journal of Biological Chemistry

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We ascribed the labeling heterogeneity to major decreases in glycerol concentration and enrichment across the liver. We concluded that [13 C]glycerol is unsuitable for tracing the contribution of gluconeogenesis to total glucose production. We now report isotopic heterogeneity of gluconeogenesis in hepatocytes, even when all cells are in contact with identical concentrations and enrichments of gluconeogenic substrates. Total rat hepatocytes were incubated with concentrations of glycerol, lactate, and pyruvate that were kept constant by substrate infusions. To modulate competition between substrates, the (glycerol)/(lactate ؉ pyruvate) infusion ratio ranged from 0.23 to 3.60. Metabolic and isotopic steady states were achieved in all cases. The apparent contribution of gluconeogenesis to glucose production (f) was calculated from the mass isotopomer distribution of glucose. When all substrates were 13 Clabeled, f was 97%, as expected in glycogen-deprived hepatocytes. As the infusion ratio ([ 13 C]glycerol)/(lactate ؉ pyruvate) increased, f increased from 73% to 94%. In contrast, as the infusion ratio (glycerol)/([ 13 C]lactate ؉ [ 13 C]pyruvate) increased, f decreased from 93% to 76%. In all cases, f increased with the rate of supply of the substrate that was labeled. Variations in f show that the 13 C labeling of triose phosphates was not equal in all hepatocytes, even when exposed to the same substrate concentrations and enrichments. We also showed that zonation of glycerol kinase activity is minor in rat liver. We conclude that zonation of other processes than glycerol phosphorylation contributes to the heterogeneity of triose phosphate labeling from glycerol in rat liver.

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Determination of the 13C-Labeling Pattern of Glucose by Gas Chromatography-Mass Spectrometry

Cited by 66 publications

References 0 publications

Effects of Dipeptidyl Peptidase-4 Inhibition on Gastrointestinal Function, Meal Appearance, and Glucose Metabolism in Type 2 Diabetes

Effects of Dipeptidyl Peptidase-4 Inhibition on Gastrointestinal Function, Meal Appearance, and Glucose Metabolism in Type 2 Diabetes

Muscle-Type Specific Intramyocellular and Hepatic Lipid Metabolism During Starvation in Wistar Rats

Limitations of the Mass Isotopomer Distribution Analysis of Glucose to Study Gluconeogenesis

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