EFFECT OF GLUCOSE ON UPTAKE OF RADIOLABELED GLUCOSE, 2-DG, AND 3-O-MGBY THE PERFUSED-RAT-LIVER

In the transition from the fasting to the fed state, plasma glucose le vels rise, and the liver converts from an organ producing glucose to o ne of storage. To determine the effect of glucose an hepatic glucose u ptake, radiolabeled glucose, 2-deoxgglucose, and 3-O-methylglucose wer e injected into perfused rat livers during different nontracer glucose levels, and the concentrations in the outflow were measured. A mathem atical 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, gl ucokinase, glucose-6-phosphatase, and the consumption of glucose 6-pho sphate were estimated. Membrane transport for all of the tracers decre ased as nontracer glucose increased, demonstrating competitive inhibit ion of the glucose transporter. In contrast, the consumption of inject ed [2-C-14]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, i ndicating that glucokinase was stimulated by glucose. Both changes wou ld lead to the increased glycogen synthesis and decreased glucose prod uction rate observed in vivo during the fasted-to-fed transition.