%0 Journal Article
%T Models for the Study of Whole-Body Glucose Kinetics: A Mathematical Synthesis
%A Leslie L. McKnight
%A Secundino Lopez
%A Anna Kate Shoveller
%A James France
%J ISRN Biomathematics
%D 2013
%R 10.1155/2013/120974
%X The maintenance of blood glucose homeostasis is complex and involves several key tissues. Most of these tissues are not easily accessible, making direct measurement of the physiological parameters involved in glucose metabolism difficult. The use of isotope tracer methodology and mathematical modeling allows indirect estimates of in vivo glucose metabolism through relatively noninvasive means. The purpose of this paper was to provide a mathematical synthesis of the models developed for describing glucose kinetics. As many of the models were developed using dogs, example data from the canine literature are presented. However, examples from the human and feline literature are also given in the absence of dog data. The glucose system is considered in both the steady and nonsteady states, and the models are examined by grouping them into schemes consisting of one, two, and three glucose compartments. Noncompartmental schemes are also considered briefly. 1. Introduction Glucose is a ubiquitous cellular fuel source for all mammalian tissues. As such, the regulation of glucose metabolism has been under extensive investigation for the past century. In healthy animals, several biological mechanisms ensure that the rate of appearance of glucose in the bloodstream tightly matches that of glucose uptake by tissues, resulting in relatively constant blood glucose concentrations irrespective of physiological condition. These control mechanisms are predominantly dictated by the energy status of the animal. In postabsorptive and fasting periods the body largely relies on endogenous glucose production via liver glycogenolysis or gluconeogenesis to maintain glucose homeostasis. In the postprandial period (or fed state) glucose uptake and utilization by tissues is increased in response to the absorption of glucose in the small intestine, giving rise to the subsequent stabilization of blood glucose concentrations. Both production and uptake are principally hormonally regulated by glucagon and insulin, but substrate availability, circulating free fatty acids (FFAs), and catecholamines (released in response to stress and/or exercise) also impact glucose metabolism. Dysregulation of glucose homeostasis, as seen in metabolic diseases including obesity and diabetes, has become a worldwide epidemic in humans [1] and companion animals [2]. These diseases share the common feature of progressive insulin resistance and hyperglycemia. The rat has been used extensively as a model for studying the etiology of these diseases (reviewed by [3]). However, the dog provides a model more
%U http://www.hindawi.com/journals/isrn.biomathematics/2013/120974/