Insulin kinetics after portal and peripheral injection of [125I] insulin. I. Data analysis and modeling

The kinetics of insulin are commonly investigated by intravenous administration of labeled hormone, whereas native insulin is removed by the liver to some extent before mixing in the systemic circulation. A mathematical model has been developed which makes it possible to interpret the experimental data obtained by peripheral plasma sampling after portal and peripheral injection of the tracer. Equations are given that allow for the computation of metabolic clearance rate, initial distribution volume, production rate, and body mass of insulin. It is demonstrated that hepatic extraction can be calculated from the difference between the clearance rate values obtained after portal and peripheral injection of the tracer; an estimate of total hepatic catabolism is also derived. The assumptions and limitations underlying this mathematical analysis are discussed.