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Am J Physiol Endocrinol Metab 279: E907-E911, 2000;
0193-1849/00 $5.00
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Vol. 279, Issue 4, E907-E911, October 2000

Effects of fructose on hepatic glucose metabolism in humans

Mirjam Dirlewanger, Philippe Schneiter, Eric Jéquier, and Luc Tappy

Institute of Physiology, University of Lausanne Medical School, 1005 Lausanne, Switzerland

Hepatic and extrahepatic insulin sensitivity was assessed in six healthy humans from the insulin infusion required to maintain an 8 mmol/l glucose concentration during hyperglycemic pancreatic clamp with or without infusion of 16.7 µmol · kg-1 · min-1 fructose. Glucose rate of disappearance (GRd), net endogenous glucose production (NEGP), total glucose output (TGO), and glucose cycling (GC) were measured with [6,6-2H2]- and [2-2H1]glucose. Hepatic glycogen synthesis was estimated from uridine diphosphoglucose (UDPG) kinetics as assessed with [1-13C]galactose and acetaminophen. Fructose infusion increased insulin requirements 2.3-fold to maintain blood glucose. Fructose infusion doubled UDPG turnover, but there was no effect on TGO, GC, NEGP, or GRd under hyperglycemic pancreatic clamp protocol conditions. When insulin concentrations were matched during a second hyperglycemic pancreatic clamp protocol, fructose administration was associated with an 11.1 µmol · kg-1 · min-1 increase in TGO, a 7.8 µmol · kg-1 · min-1 increase in NEGP, a 2.2 µmol · kg-1 · min-1 increase in GC, and a 7.2 µmol · kg-1 · min-1 decrease in GRd (P < 0.05). These results indicate that fructose infusion induces hepatic and extrahepatic insulin resistance in humans.

endogenous glucose production; glucose cycling; glycogen synthesis; insulin resistance; liver


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