title: Resolving the sources of plasma glucose excursions following a glucose tolerance test in the rat with deuterated water and [U-13C]glucose.
abstract: Sources of plasma glucose excursions (PGE) following a glucose tolerance test enriched with [U-(13)C]glucose and deuterated water were directly resolved by (13)C and (2)H Nuclear Magnetic Resonance spectroscopy analysis of plasma glucose and water enrichments in rat. Plasma water (2)H-enrichment attained isotopic steady-state within 2-4 minutes following the load. The fraction of PGE derived from endogenous sources was determined from the ratio of plasma glucose position 2 and plasma water (2)H-enrichments. The fractional gluconeogenic contributions to PGE were obtained from plasma glucose positions 2 and 5 (2)H-positional enrichment ratios and load contributions were estimated from plasma [U-(13)C]glucose enrichments. At 15 minutes, the load contributed 26±5% of PGE while 14±2% originated from gluconeogenesis in healthy control rats. Between 15 and 120 minutes, the load contribution fell whereas the gluconeogenic contribution remained constant. High-fat fed animals had significant higher 120-minute blood glucose (173±6 mg/dL vs. 139±10 mg/dL, p<0.05) and gluconeogenic contributions to PGE (59±5 mg/dL vs. 38±3 mg/dL, p<0.01) relative to standard chow-fed controls. In summary, the endogenous and load components of PGE can be resolved during a glucose tolerance test and these measurements revealed that plasma glucose synthesis via gluconeogenesis remained active during the period immediately following a glucose load. In rats that were placed on high-fat diet, the development of glucose intolerance was associated with a significantly higher gluconeogenic contribution to plasma glucose levels after the load.
authors.affiliation: Intermediary Metabolism Group, Center for Neurosciences and Cell Biology, Coimbra, Portugal.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Delgado
authors.forename: Cristina
authors.initials: C
authors.lastname: Barosa
authors.forename: Patrícia M
authors.initials: PM
authors.lastname: Nunes
authors.forename: Sebastián
authors.initials: S
authors.lastname: Cerdán
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
authors.forename: John G
authors.initials: JG
authors.lastname: Jones
mesh_terms: D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D017666:Deuterium Oxide / Q000737:chemistry; D004041:Dietary Fats / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D005947:Glucose / Q000031:analogs & derivatives / Q000378:metabolism; D005951:Glucose Tolerance Test / Q000379:methods*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006003:Glycogen / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D005636:Fructosephosphates; D005958:Glucosephosphates; D014867:Water; C028223:1,2-O-isopropylidene-D-glucofuranose; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D006003:Glycogen; C031590:glucose-1-phosphate; D005947:Glucose; D017666:Deuterium Oxide