The isolated perfused rat liver preparation has been used to study the effects of fasting and liberal feeding against the action of sulfonylureas on hepatic metabolism.
Livers were taken from male rats of the Wistar strain weighing 200 to 300g. They were fed ad libitum or fasted for 18 hours prior to perfusion. The initial recirculating solution used was 250 ml with Krebs-Ringer bicarbonate buffer containing 2.5% bovine albumin, 10 mM glucose and 25% bovine erythrocytes prepared as reported previously. Tolbutamide was added in the medium after 30 minutes pre-perfusion. However, exogenous lactate was perfused without pre-perfusion.
1) It was found that tolbutamide directly suppressed glucose production and ketone body formation by the isolated fasted rat liver, but that it failed to reduce these metabolites in the fed rat liver.
2) Glucose production was minimally increased in livers from fasted or fed rats perfused with lactate. It was found that lactate markedly suppressed ketogenesis in livers from fasted rats, but that it increased ketogenesis in livers from fed rats.
3) The degree of utilization by the livers of added lactate was immediately and markedly increased after the start of perfusion in livers from fasted rats. However, there was a lag time before the utilization of added lactate started in livers from fed rats as compared with those from fasted rats. No differences were found as regards changes in LIP ratio between fasted and fed rat livers.