GLUCOSE DIFFUSION IN PANCREATIC-ISLETS OF LANGERHANS

We investigate the time required for glucose to diffuse through an iso lated pancreatic islet of Langerhans and reach an equilibrium. This qu estion is relevant in the context of in vitro electrophysiological stu dies of the response of an islet to step changes in the bath glucose c oncentration. Islet cells are electrically coupled by gap junctions, s o nonuniformities in islet glucose concentration may be reflected in t he activity of cells on the islet periphery, where electrical recordin gs are made. Using a mathematical model of hindered glucose diffusion, we investigate the effects of the islet porosity and the permeability of a surrounding layer of acinar cells. A major factor in the determi nation of the equilibrium time is the transport of glucose into islet beta-cells, which removes glucose from the interstitial spaces where d iffusion occurs. This transport is incorporated by using a model of th e GLUT-2 glucose transporter. We find that. several minutes are requir ed for the islet to equilibrate to a 10 mM change in bath glucose, a t ypical protocol in islet experiments. It is therefore likely that in e lectrophysiological islet experiments the glucose distribution is nonu niform for several minutes after a step change in bath glucose. The de lay in glucose penetration to the inner portions of the islet may be a major contributing Tractor to the 1-2-min delay in islet electrical a ctivity typically observed after bath application of a stimulatory con centration of glucose.