The isolated perfused rat liver preparation has been used for study of the effects of prolonged fasting against the action of sulfonylureas and exogenous lactate on hepatic metabolism.
Livers were taken from several male rats of the Wistar strain weighing 200 to 300g. They were made to fast 72 hours prior to use. The volume of the initial recirculating solution used was 250ml of Krebs-Ringer bicarbonate buffer containing 2.5% bovine albumin, 10mM glucose and 25% bovine erythrocytes prepared as reported previously. Tolbutamide was added to the medium after 30 minutes pre-perfusion. However, exogenous lactate was perfused without preperfusion.
1) Glucose production from the added lactate, by the prolonged fasted livers was observed during perfusion. Without adding exogenous lactate, glucose production was found to last only 30 minutes after perfusion. It was found that tolbutamide directly suppressed glucose production from exogenous lactate.
2) Exogenous lactate and tolbutamide markedly suppressed ketogenesis. However, no additive effect for the suppression of ketogenesis was found between exogenous lactate and tolbutamide.
3) The degree of utilization by the livers of added lactate markedly went down with tolbutamide. No differences, however, were found in changes in the Lactate/Pyruvate ratio with or without tolbutamide.