Mathematical modelling of alpha- and beta-D-glucose metabolism in pancreatic islets exposed to equilibrated D-glucose.

Abstract

Based on the measurement of 3HOH generation from the alpha- and beta-anomer of D-[2-3H]glucose and D-[5-3H] glucose by rat pancreatic islets, it was recently proposed that alpha-D-glucose 6-phosphate may undergo enzyme-to-enzyme channelling between hexokinase isoenzymes and phosphoglucoisomerase. Taking into account the results of such measurements, the present study aims at defining a model for the metabolism of alpha- and beta-D-glucose in islets exposed to 2.8 or 8.3 mM equilibrated D-glucose. It is proposed that, whilst keeping the activity of free phosphoglucoisomerase at its physiological value, all available experimental data can be adequately reproduced in a model in which all molecules of alpha-D-glucose 6-phosphate, whether unlabelled or tritiated on their C2 carbon atom, undergo, without isotopic discrimination, the postulated enzyme-to-enzyme channelling process. In such a model, the fractional intermolecular transfer of tritium at the phosphoglucoisomerase level amounts to 26%, suggesting that the intrinsic catalytic properties of the enzyme may be slightly different in the proposed metabolon than that prevailing for the unbound enzyme. These findings thus afford further support to the concept that alpha-D-glucose 6-phosphate, as distinct from beta-D-glucose 6-phosphate, is tunnelled, in rat pancreatic islets, in the sequence of reactions catalyzed by hexokinase isoenzymes, phosphoglucoisomerase and, possibly, phosphofructokinase.