title: Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects.
abstract: During feeding, dietary galactose is a potential source of hepatic glycogen synthesis; but its contribution has not been measured to date. In the presence of deuterated water ((2)H(2)O), uridine diphosphate (UDP)-glucose derived from galactose is not enriched, whereas the remainder derived from glucose-6-phosphate (G6P) is enriched in position 2 to the same level as body water, assuming complete G6P-fructose-6-phosphate (F6P) exchange. Hence, the difference between UDP-glucose position 2 and body water enrichments reflects the contribution of galactose to glycogen synthesis relative to all other sources. In study 1, G6P-F6P exchange in 6 healthy subjects was quantified by supplementing a milk-containing breakfast meal with 10 g of [U-(2)H(7)]glucose and quantifying the depletion of position 2 enrichment in urinary menthol glucuronide. In study 2, another 6 subjects ingested (2)H(2)O and acetaminophen followed by an identical breakfast meal with 10 g of [1-(13)C]glucose to resolve direct/indirect pathways and galactose contributions to glycogen synthesis. Metabolite enrichments were determined by (2)H and (13)C nuclear magnetic resonance. In study 1, G6P-F6P exchange approached completion; therefore, the difference between position 2 and body water enrichments in study 2 (0.20% ± 0.03% vs 0.27% ± 0.03%, P < .005) was attributed to galactose glycogenesis. Dietary galactose contributed 19% ± 3% to glycogen synthesis. Of the remainder, 58% ± 5% was derived from the direct pathway and 22% ± 4% via the indirect pathway. The contribution of galactose to hepatic glycogen synthesis was resolved from that of direct and indirect pathways using a combination of (2)H(2)O and [1-(13)C]glucose tracers.
authors.affiliation: Biophysics and Biomedical NMR, Center for Neurosciences and Cell Biology, University of Coimbra, 3001-401 Coimbra, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Barosa
authors.forename: Claudia
authors.initials: C
authors.lastname: Silva
authors.forename: Ana
authors.initials: A
authors.lastname: Fagulha
authors.forename: Luísa
authors.initials: L
authors.lastname: Barros
authors.forename: M Madalena
authors.initials: MM
authors.lastname: Caldeira
authors.forename: Manuela
authors.initials: M
authors.lastname: Carvalheiro
authors.forename: John G
authors.initials: JG
authors.lastname: Jones
mesh_terms: D000328:Adult; D000818:Animals; D002247:Carbon Isotopes / Q000493:pharmacokinetics; D017666:Deuterium Oxide / Q000493:pharmacokinetics; D004435:Eating / Q000502:physiology*; D005260:Female; D005636:Fructosephosphates / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000493:pharmacokinetics; D019298:Glucose-6-Phosphate / Q000378:metabolism; D020719:Glucuronides / Q000378:metabolism; D006262:Health; D006801:Humans; D008112:Liver Glycogen / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D008892:Milk / Q000378:metabolism / Q000502:physiology; D014018:Tissue Distribution; D055815:Young Adult
chemical_list: D002247:Carbon Isotopes; D005636:Fructosephosphates; D020719:Glucuronides; D008112:Liver Glycogen; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D005947:Glucose; D017666:Deuterium Oxide