Continuous low-dose fructose infusion does not reverse glucagon-mediated decrease in hepatic glucose utilization

Abstract

An adaptation to continuous total parenteral nutrition (TPN; 75% of nonprotein calories as glucose) is the liver becomes a major consumer of glucose with lactate release as a by-product. The liver is able to further increase liver glucose uptake when a small dose of fructose is acutely infused via the portal system. Glucagon, commonly elevated during inflammatory stress, is a potent inhibitor of glucose uptake by the liver during TPN. The aim was to determine if continuous fructose infusion could overcome the glucagon-mediated decrease in hepatic glucose uptake. Studies were performed in conscious, insulin-treated, chronically catheterized, pancreatectomized dogs that adapted to TPN for 33 hours. They were then assigned to 1 of 4 groups: TPN (C), TPN + fructose (4.4 μmol kg(-1) min(-1); F), TPN + glucagon (0.2 pmol kg(-1) min(-1); GGN), or TPN + fructose and glucagon (F + GGN) for an additional 63 hours (33-96 hours). Insulin, fructose, and glucagon were infused into the portal vein. During that period, all animals received a fixed insulin infusion of 0.4 mU·kg(-1)·min(-1) (33-96 hours); and the glucose infusion rates were adjusted to maintain euglycemia (6.6 mmol/L). Continuous fructose infusion was unable to further enhance net hepatic glucose uptake (in micromoles per kilogram per minute) (31.1 ± 2.8 vs 36.1 ± 5.0; C vs F), nor was it able to overcome glucagon-mediated decrease in net hepatic glucose uptake (10.0 ± 4.4 vs 12.2 ± 3.9; GGN vs F + GGN). In summary, continuous fructose infusion cannot augment liver glucose uptake during TPN; nor can it overcome the inhibitory effects of glucagon.

Figure 1

Arterial plasma glucose concentration, net hepatic glucose uptake and net hepatic glucose fractional extraction in chronically catheterized conscious dogs receiving TPN (C), TPN and fructose (F), TPN and glucagon (GGN), or TPN and both F and GGN (F+GGN). NHGU (F+GGN vs C ^* p<0.005, F+GGN vs F ⁺ p<0.005; G vs C ^a p<0.005, GGN vs F ^b p<0.005). Glucose fractional extraction (F+GGN vs C ^* p<0.005, F+GGN vs F ⁺ p<0.005; GGN vs C ^a p<0.005, GGN vs F ^b p<0.005) Data are expressed as mean±SEM.