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Inclusion of low amounts of fructose with an intraportal glucose load increases net hepatic glucose uptake in the presence of relative insulin deficiency in dog

Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee

Submitted 23 August 2004 ; accepted in final form 22 January 2005

The effect of small amounts of fructose on net hepatic glucose uptake (NHGU) during hyperglycemia was examined in the presence of insulinopenia in conscious 42-h fasted dogs. During the study, somatostatin (0.8 µg·kg^–1·min^–1) was given along with basal insulin (1.8 pmol·kg^–1·min^–1) and glucagon (0.5 ng·kg^–1·min^–1). After a control period, glucose (36.1 µmol·kg^–1·min^–1) was continuously given intraportally for 4 h with (2.2 µmol·kg^–1·min^–1) or without fructose. In the fructose group, the sinusoidal blood fructose level (nmol/ml) rose from <16 to 176 ± 11. The infusion of glucose alone (the control group) elevated arterial blood glucose (µmol/ml) from 4.3 ± 0.3 to 11.2 ± 0.6 during the first 2 h after which it remained at 11.6 ± 0.8. In the presence of fructose, glucose infusion elevated arterial blood glucose (µmol/ml) from 4.3 ± 0.2 to 7.4 ± 0.6 during the first 1 h after which it decreased to 6.1 ± 0.4 by 180 min. With glucose infusion, net hepatic glucose balance (µmol·kg^–1·min^–1) switched from output (8.9 ± 1.7 and 13.3 ± 2.8) to uptake (12.2 ± 4.4 and 29.4 ± 6.7) in the control and fructose groups, respectively. Average NHGU (µmol·kg^–1·min^–1) and fractional glucose extraction (%) during last 3 h of the test period were higher in the fructose group (30.6 ± 3.3 and 14.5 ± 1.4) than in the control group (15.0 ± 4.4 and 5.9 ± 1.8). Glucose 6-phosphate and glycogen content (µmol glucose/g) in the liver and glucose incorporation into hepatic glycogen (µmol glucose/g) were higher in the fructose (218 ± 2, 283 ± 25, and 109 ± 26, respectively) than in the control group (80 ± 8, 220 ± 31, and 41 ± 5, respectively). In conclusion, small amounts of fructose can markedly reduce hyperglycemia during intraportal glucose infusion by increasing NHGU even when insulin secretion is compromised.

diabetes mellitus; hyperglycemia; hyperinsulinemia

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