Effects of high extracellular K+ concentrations, diazoxide and/or Ca2+ deprivation upon D-glucose metabolism in pancreatic islets

A rise in D-glucose concentration may augment insulin release independently of changes in Kt conductance or Ca2+ influx in pancreatic islet cells, the insulinotropic action of the hexose remaining dependent on an increased ge neration of high-energy phosphates. In the present study, therefore, it was investigated to which extent the procedures currently used to assess the m odalities of the secretory response to D-glucose independent of its effect on ATP-sensitive K+ channels and Ca2+ inflow may themselves affect the cata bolism of the hexose in isolated rat pancreatic islets. 4 rise in the extra cellular K+ concentration from 5 to 30 or 60 mM failed to significantly aff ect the metabolism of D-glucose. At 90 mM K+, however, the maximal velocity of the glycolytic flux was decreased and the apparent K-m for D-glucose lo wered, without an obvious alteration of the preferential stimulation of oxi dative mitochondrial events in response to a rise in D-glucose concentratio n. Such a preferential stimulation was abolished, however, either by diazox ide at a low, but not high, K+ concentration or by Ca2+ deprivation, in the absence or presence of diazoxide, at a high Ki concentration. It is specul ated that these metabolic changes may be attributable, in part at least, to an altered activity of key cytosolic (e.g. pyruvate kinase) and mitochondr ial (e.g. FAD-linked glycerophosphate dehydrogenase) enzymes. (C) 1999 Else vier Science B.V. All rights reserved.