Effects of high extracellular K(+) concentrations, diazoxide and/or Ca(2+) deprivation upon D-glucose metabolism in pancreatic islets.

A rise in D-glucose concentration may augment insulin release independently of changes in K(+) conductance or Ca(2+) influx in pancreatic islet cells, the insulinotropic action of the hexose remaining dependent on an increased generation of high-energy phosphates. In the present study, therefore, it was investigated to which extent the procedures currently used to assess the modalities of the secretory response to D-glucose independent of its effect on ATP-sensitive K(+) channels and Ca(2+) inflow may themselves affect the catabolism of the hexose in isolated rat pancreatic islets. A rise in the extracellular K(+) concentration from 5 to 30 or 60 mM failed to significantly affect 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 lowered, without an obvious alteration of the preferential stimulation of oxidative mitochondrial events in response to a rise in D-glucose concentration. Such a preferential stimulation was abolished, however, either by diazoxide at a low, but not high, K(+) concentration or by Ca(2+) deprivation, in the absence or presence of diazoxide, at a high K(+) concentration. It is speculated that these metabolic changes may be attributable, in part at least, to an altered activity of key cytosolic (e.g. pyruvate kinase) and mitochondrial (e.g. FAD-linked glycerophosphate dehydrogenase) enzymes.