Effect of glucose on uptake of radiolabeled glucose, 2-DG, and 3-O-MG by the perfused rat liver.

In the transition from the fasting to the fed state, plasma glucose levels rise, and the liver converts from an organ producing glucose to one of storage. To determine the effect of glucose on hepatic glucose uptake, radiolabeled glucose, 2-deoxyglucose, and 3-O-methylglucose were injected into perfused rat livers during different nontracer glucose levels, and the concentrations in the outflow were measured. A mathematical model was developed that described the behavior of the injected compounds as they traveled through the liver and was used to simulate and fit the experimental results. The rates of membrane transport, glucokinase, glucose-6-phosphatase, and the consumption of glucose 6-phosphate were estimated. Membrane transport for all of the tracers decreased as nontracer glucose increased, demonstrating competitive inhibition of the glucose transporter. In contrast, the consumption of injected [2-14C]glucose increased when glucose was elevated, demonstrating that glucose caused an activation of enzyme activity that overcame the competitive inhibition of transport and phosphorylation. When glucose was elevated, the rate coefficient of glucokinase did not decrease, indicating that glucokinase was stimulated by glucose. Both changes would lead to the increased glycogen synthesis and decreased glucose production rate observed in vivo during the fasted-to-fed transition.