Calcium and pancreatic beta-cell function. 5. Mobilisation of a glucose-stimulated pool of intracellular 45Ca by metabolic inhibitors and the ionophore A-23187.

Glucose is believed to stimulate incorporation of calcium into the secretory granules of the pancreatic beta-cells. The mechanism of the glucose-stimulated accumulation of calcium in the granule pool was evaluated by measuring fluxes of 45Ca in beta-cell-rich pancreatic islets microdissected from ob/ob-mice. The incorporation of lanthanum-nondisplaceable 45Ca in response to phosphate in being suppressed by 10 micrometer antimycin A, 0.3 mM 2,4-dinitrophenol or 1 mM N-ethylmaleimide. Exposure to each of these metabolic inhibitors also resulted in a protracted efflux of the glucose-sensitive 45Ca under conditions when neither the 45Ca incorporated in the presence of 3 mM glucose nor in response to phosphate was significantly affected. The glucose-stimulated intracellular 45Ca existed in a state allowing it to be washed out with the ionophore A-23187. The results suggest that the glucose-stimulated incorporation of calcium into the secretory granules is mediated by transport against a concentration gradient into the granule sac.