Glucose and insulin dynamics in the anaesthetized dog: a mathematical modeling study

A combined circulation and organs model of glucose and insulin dynamics is presented. The model is based on physiological parameters, incorporating blood and plasma flow rates, circulatory paths, intra-and extra-vascular glucose and insulin spaces, as well as the specific organs and tissues involved both with insulin disappearance and with glucose production or uptake. Its simulations readily lend themselves to physiological interpretation. To explore its validity, the model was assigned parameters typical of a 12 kg dog and was arranged to accept known glucose and insulin infusions from four different experiments on such diabetic animals. It predicted the observed glucose and insulin concentrations as well as total uptake rates for both moieties. This confirmed the ability of the model to predict with consistency the group mean outcomes of these four experiments when differing routes (portal or peripheral) of infusion were applied. Excellent agreement for most studies was achieved while the need for including more sophisticated dynamics of glucose transport in the liver or into erythrocytes was identified. The model isolates glucose uptake in the periphery, the liver, the brain and the gut and allows a direct comparison of glucose disposal along various routes. Thus the total amount of glucose uptake by peripheral, insulin-dependent tissues is directly calculated to be 22-28% of an intravenous glucose load, regardless of its route of infusion.