Interaction between D-glucose and Ca2+ in the priming of the pancreatic B-cell.

Prior exposure of the endocrine pancreas to a high as distinct from low concentration of D-glucose is thought to result in either an increased (priming action) or decreased (glucotoxic action) responsiveness of the B-cell to a subsequent stimulation by the hexose. In order to investigate these phenomena in vitro, rat pancreatic islets were preincubated for 180 min at increasing concentrations of D-glucose in the absence or presence of extracellular Ca2+, and then stimulated with the hexose (16.7 mM) in the absence or presence of theophylline (1.4 mM). Under these conditions, a dose-related priming action of D-glucose was observed without evidence of any glucotoxic effect. The priming effect persisted when the islets were preincubated in the absence of Ca2+, although such a prior Ca2+ deprivation itself decreased the magnitude of the further secretory response to D-glucose. The presence of theophylline in the final incubation medium minimized but failed to abolish the priming action of D-glucose. It is proposed that Ca2+ and cyclic AMP availability may interfere with the priming action of D-glucose. Moreover, the present results suggest that a more stringent or more prolonged pretreatment of the islet cells may be required in order to allow for the occurrence of the postulated cytotoxic action of D-glucose upon the pancreatic B-cell.