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

D Massillon, W Chen, M Hawkins… - American Journal …, 1995 - journals.physiology.org
D Massillon, W Chen, M Hawkins, R Liu, N Barzilai, L Rossetti
American Journal of Physiology-Endocrinology and Metabolism, 1995journals.physiology.org
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 …
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.
American Physiological Society