Minimal model of glucose/insulin dynamics in the intact organism. A novel approach for evaluation of factors controlling glucose tolerance.

One of the major goals in metabolic physiology is the development of methods to quantify specific processes involved in carbohydrate metabolism regulation in the intact organism. In this paper we propose a novel non-invasive (as compared to other techniques) approach for estimating in vivo glucose-insulin dynamic interactions. The rationale of the approach lies in the interpretation of glucose/insulin dynamic data, obtained after a system perturbation, with two mathematical models: particular attention is devoted to the selection of these two models. A minimal, or parsimonious, modelling strategy is proposed, that is, the two models are selected out of two series of physiologically based models, respectively; six of glucose disappearance; and six of insulin secretion and kinetics, according to a set of specific criteria. The two chosen minimal models of glucose metabolism and insulin secretion permit a quantitative insight into the metabolic state of an intact organism by providing accurate estimates of parameters such as insulin sensitivity and pancreatic sensitivity to glucose. Possible physiological and clinical uses of the two models for in vivo quantitative studies of glucose/insulin interactions are discussed, together with the insight that these models seem to provide into the intimate nature of metabolic control