A circulation and organs model for insulin dynamics.

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Abstract
A Circulation and Organs Model for Insulin Dynamics (COMID) is presented. The model is based on physiological parameters, incorporating plasma flow rates, circulatory paths, intra- and extravascular insulin spaces, and specific tissues and organs involved with insulin disappearance. As such, its simulations readily lend themselves to physiological interpretation. To explore its validity, COMID was assigned parameters typical of a 12 kg beagle and was arranged to accept known insulin infusions from 4 different experiments on such diabetic dogs. It predicted the resulting total insulin degradation rates as well as the accompanying peripheral insulin concentrations. This confirmed the ability of the model to predict with consistency the group mean outcomes of these 4 different experiments with the diabetic dogs when differing routes (portal or peripheral) and waveforms (simple and complex) of insulin infusion were applied. The excellent agreement for all cases was achieved only when a nonlinear function describing insulin disappearance was chosen. Because the model proved consistent, it was used to compute insulin degradation in the liver, kidneys and peripheral tissues and predicted that degradation in the periphery dominates when insulin is infused peripherally. In the light of this prediction, the data raise the possibility that the peripheral i.v. route for insulin infusion may have undesirable effects that merit careful examination by further experimentation.