Insulin Removal by Isolated Perfused Rat Liver

Removal of unlabeled insulin was studied in the perfused rat liver. Insulin removal followed first-order kinetics over the range of concentrations found in the portal vein of postabsorptive rats, but deviated from first-order kinetics in experiments with a wider concentration range. Clearance was more than twice as great at concentrations normally found in the portal vein in the postabsorptive state (0.40-1.1nM or about 60-100 muU/ml) than at concentrations expected after pancreatic stimulation (4.5-7.0 nM). Saturation of the liver's capacity to remove insulin, however, was not observed even at higher levels. Insulin clearance diminished when the flow rate was reduced. It was not significantly altered by prolonged starvation. Our results suggest that when the insulin concentration is high a greater percentage escapes hepatic degradation then when it is low. Hepatic insulin clearance is in part dependent on the portal flow rate. The kinetics of insulin removal by the perfused liver cannot be accounted for by the properties of insulin-degrading enzymes described by others.