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Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

¹ Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee
² Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut

Intraportal infusion of small amounts of fructose markedly augmented net hepatic glucose uptake (NHGU) during hyperglycemic hyperinsulinemia in conscious dogs. In this study, we examined whether the inclusion of catalytic amounts of fructose with a glucose load reduces postprandial hyperglycemia and the pancreatic ß-cell response to a glucose load in conscious 42-h-fasted dogs. Each study consisted of an equilibration (-140 to -40 min), control (-40 to 0 min), and test period (0–240 min). During the latter period, glucose (44.4 µmol · kg^-1 · min^-1) was continuously given intraduodenally with (2.22 µmol · kg^-1 · min^-1) or without fructose. The glucose appearance rate in portal vein blood was not significantly different with or without the inclusion of fructose (41.3 ± 2.7 vs. 37.3 ± 8.3 µmol · kg^-1 · min^-1, respectively). In response to glucose infusion without the inclusion of fructose, the net hepatic glucose balance switched from output to uptake (from 10 ± 2 to 11 ± 4 µmol · kg^-1 · min^-1) by 30 min and averaged 17 ± 6 µmol · kg^-1 · min^-1. The fractional extraction of glucose by the liver during the infusion period was 7 ± 2%. Net glycogen deposition was 2.44 mmol glucose equivalent/kg body wt; 49% of deposited glycogen was synthesized via the direct pathway. Net hepatic lactate production was 1.4 mmol/kg body wt. Arterial blood glucose rose from 4.1 ± 0.2 to 7.3 ± 0.4 mmol/l, and arterial plasma insulin rose from 42 ± 6 to 258 ± 66 pmol/l at 30 min, after which they decreased to 7.0 ± 0.5 mmol/l and 198 ± 66 pmol/l, respectively. Arterial plasma glucagon decreased from 54 ± 7 to 32 ± 3 ng/l. In response to intraduodenal glucose infusion in the presence of fructose, net hepatic glucose balance switched from 9 ± 1 µmol · kg^-1 · min^-1 output to 12 ± 3 and 28 ± 5 µmol · kg^-1 · min^-1 uptake by 15 and 30 min, respectively. The average NHGU (28 ± 5 µmol · kg^-1 · min^-1) and fractional extraction during infusion period (12 ± 2%), net glycogen deposition (3.68 mmol glucose equivalent/kg body wt), net hepatic lactate production (3.27 mmol/kg), and glycogen synthesis via the direct pathway (68%) were significantly higher (P < 0.05) compared to that in the absence of fructose. The increases in arterial blood glucose (from 4.4 ± 0.1 to 6.4 ± 0.2 mmol/l at 30 min) and arterial plasma insulin (from 48 ± 6 to 126 ± 30 pmol/l at 30 min) were significantly smaller (P < 0.05). In summary, the inclusion of small amounts of fructose with a glucose load augmented NHGU, increased hepatic glycogen synthesis via the direct pathway, and augmented hepatic glycolysis. As a result, postprandial hyperglycemia and insulin release by the pancreatic ß-cell were reduced. In conclusion, catalytic amounts of fructose have the ability to improve glucose tolerance.

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