The effect of xenobiotic acetylation on interorgan metabolism of glucose in fasted rats

The effect of cytosolic acetylation on interorgan glucose metabolism was studied by arteriovenous (AV) difference and tracer kinetic techniques in fasted, ketamine-anesthetized rats. The administration of sulfamethazine (SMZ, 2 mmol/kg, i.p.) resulted in 39% and 313% increases in hepatic contents of glucose and lactate, respectively. Plasma concentrations of glucose and lactate in the aorta, portal vein and hepatic vein also increased (33-43% for glucose, and 86-200% for lactate). Net hepatic release of glucose was not significantly different from the control. Net hepatic uptake of lactate increased 72-151% in the SMZ-treated rats. The concentration and hepatic gradient of alanine were little changed in the SMZ-treated rats. The rates of turnover for plasma glucose, estimated from [3-³H]-glucose, were not significantly different between the control and SMZ-treated rats. The rate of glucose recycling, estimated from the difference in the rates of turnover between [3-³H]- and [U-¹⁴C]-glucose, decreased by 42% in the SMZ-treated rats. Muscle glycogen in the SMZ-treated rats also decreased (33%). In conclusion, our data indicate that cytosolic acetylation can affect not only ketogenesis, as we have previously reported, but also interorgan metabolism of glucose. Although direct evidence is not available, Increases in the levels of plasma and liver glucose suggest that gluconeogenesis is increased in the SMZ-treated rats. A net loss of lactate from muscle glycogen store to the liver is indicated by the increase in hepatic uptake of lactate and the decrease in the rate of glucose recycling in the rats treated with SMZ.