Relationship of Hepatic Glucose Uptake to Intrahepatic Glucose Concentration in Fasted Rats After Glucose Load

Glucose concentration gradients across the liver and hepatic blood flow were measured to characterize the relationship of hepatic glucose uptake to hepatic glucose concentration for 240 min after administration of a large oral glucose load to fasted rats. Extraction of glucose occurred only transiently, from 20 to 80 min after glucose administration. The liver changed from net glucose output to net glucose removal only when the intracellular hepatic glucose concentration exceeded 12.5 μmol/ml water. Even when arteriovenous glucose concentrations gradients were compatible with net direct hepatic uptake of glucose, the hepatic glucose concentration always exceeded the inflow glucose concentration. These data indicate that direct glucose uptake occurred against a concentration gradient when the liver is considered as a whole. The hepatic intracellular-to-extracellular glucose concentration gradient changed very little, suggesting that this is not being regulated by glucose, insulin, or other effectors. The mechanism by which the hepatic glucose concentration and net hepatic glucose uptake versus output are coordinated is unknown. The rate of glycogen synthesis was linear for 120 min after administration of the glucose load. This occurred in the presence of direct uptake of glucose early in the time course and later in the presence of net glucose output by the liver. Net direct uptake of glucose by the liver could account for, at most, 37–55% of the glycogen formed. Fractional extraction of both lactate and alanine decreased after glucose was given, but net hepatic uptake of these metabolites could account for 33–49 and 7–10%, respectively, of the glycogen formed, depending on plasma versus blood water flow. Although net glucose, lactate, and alanine uptake could account for netglycogen formation, uptake of these substrates alone could not account for net glucose as well as glycogen synthesis after glucose was given.