Kinetics of insulin clearance by the liver in perfused liver-pancreas.

The relationship between hepatic insulin extraction velocity and portal plasma insulin concentration was assessed using in situ perfused liver-pancreas preparations from rats fasted 24 or 48 hours. During hepatic transit of the first phase of glucose-stimulated insulin secretion, hepatic extraction velocities followed first order kinetics for all insulin concentrations observed (less than 1 to 17 ng/ml). During the second phase of insulin release, saturation of the insulin removal process occurred at insulin concentrations between 12 and 14 ng/ml. At non-saturating insulin levels, livers from rats fasted 24 hours clear insulin at about 4.0 ml/min corresponding to an extraction ratio of 52%. In contrast, livers of liver-pancreases from 48 hour fasted rats clear insulin at 2.4 ml/min with an extraction ratio of 31%.