Quantitation of hepatic glucose fluxes and pathways of hepatic glycogen synthesis in conscious mice

D. Massillon, W. Chen, M. Hawkins, R. Liu, N. Barzilai, L. Rossetti

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26 Scopus citations


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 (~800 μU/ml); 2) hyperglycemic (15.3 ± 0.4 mM) hyperinsulinemia (~800 μU/ml). All mice received an infusion of [3- 3H]glucose and (U-14C]lactate. Basal hepatic glucose production (HGP) averaged ~ 170 μmol · kg-1 · min-1 in both groups. During euglycemic and hyperglycemic hyperinsulinemia, HGP decreased by 53% (to 76.7 ± 11.1 μmol · kg-1 · min-1; P < 0.01) and 74% (to 43.3 ± 7.2 μmol · 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.

Original languageEnglish (US)
Pages (from-to)E1037-E1043
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number6 32-6
StatePublished - 1995


  • gluconeogenesis
  • glucose cycling
  • glycogenolysis
  • hepatic glucose production
  • insulin action

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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