A quasi-equilibrium reduced model of pancreatic insulin secretion.

Abstract

Much attention has been devoted in the last few decades to mathematical models of insulin secretion, in order to better understand the regulation of glycemia and its derangements. The glucose-insulin homeostatic mechanism is so complex and gives rise to such diverse behavior following perturbations that different models had been published, which reproduced the results of single experiments. More recently, a unifying model of pancreatic insulin secretion was proposed, which is able to account, with a single value of the (meta)parameters, for the wide array of clinically observed behavior. This model explicitly represented the pulsatile nature of the many pancreatic hormone-secreting firing units: the price to pay for its flexibility and performance is the very high dimensionality (hundreds of thousand equations) of the corresponding dynamical system. Clearly, it would be desirable to reduce this model to a much simpler form while retaining its power to reproduce heterogeneous phenomena. The present work reviews the qualitative behavior of this pancreas pulsatile model and offers some insight into its reduction in equilibrium and quasi-equilibrium conditions, also considering single-shot (non-repeated) glucose jumps from an approximately resting condition (such as would occur in standard Intra-Venous bolus dosing of glucose during diabetes diagnostic maneuvers). The resulting quasi-steady-state model can be further endowed with additional lower-order dynamics to also approximate transient behavior. Although a more accurate reduction of the original pulsatile model is left to further investigation, numerical results confirm the biomedical applicability of the formulation already obtained.