title: Quantitation of hepatic glucose fluxes and pathways of hepatic glycogen synthesis in conscious mice.
abstract: Mice were studied with the euglycemic hyperinsulinemic and the hyperglycemic clamp techniques after a 6-h fast: 1) euglycemic (6.7 +/- 0.2 mM) hyperinsulinemia (approximately 800 microU/ml); 2) hyperglycemic (15.3 +/- 0.4 mM) hyperinsulinemia (approximately 800 microU/ml). All mice received an infusion of [3-3H]glucose and [U-14C]lactate. Basal hepatic glucose production (HGP) averaged approximately 170 mumol.kg-1.min-1 in both groups. During euglycemic and hyperglycemic hyperinsulinemia, HGP decreased by 53% (to 76.7 +/- 11.1 mumol.kg-1.min-1; P < 0.01) and 74% (to 43.3 +/- 7.2 mumol.kg-1.min-1; P < 0.01), respectively. Hyperglycemia increased glucose cycling (by 2.1-fold; P < 0.01) and the contribution of gluconeogenesis to HGP (88 vs. 43%; P < 0.01) while decreasing that of glycogenolysis (12 vs. 57%; P < 0.01). The percentage of neosynthetized hepatic glycogen formed via the direct pathway was markedly increased during hyperglycemia (53 +/- 2% vs. 23 +/- 3%; P < 0.01): These data indicate that the assessment of hepatic glucose fluxes can be accomplished in conscious unrestrained mice and that, in the presence of hyperinsulinemia, hyperglycemia causes 1) a further inhibition of HGP mainly via inhibition of glycogenolysis and increase in hepatic glucose cycling; and 2) about a fivefold stimulation in the direct pathway of hepatic glycogen formation.
authors.affiliation: Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
authors.forename: D
authors.initials: D
authors.lastname: Massillon
authors.forename: W
authors.initials: W
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Hawkins
authors.forename: R
authors.initials: R
authors.lastname: Liu
authors.forename: N
authors.initials: N
authors.lastname: Barzilai
authors.forename: L
authors.initials: L
authors.lastname: Rossetti
mesh_terms: D000818:Animals; D005240:Feasibility Studies; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006003:Glycogen / Q000096:biosynthesis*; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007328:Insulin; D006003:Glycogen; D005947:Glucose