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

Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog Masakazu Shiota 1 , Mary Courtney Moore 1 , Pietro Galassetti 1 , Michael Monohan 1 , Doss W. Neal 1 , Gerald I. Shulman 2 and Alan D. Cherrington 1 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 Abstract 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 β-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 ±