Quinacrine accumulation in pancreatic islet cells of rat and mouse: relationship to functional activity and effects on basal and stimulated insulin secretion

Abstract

The fluorescent acridine derivative, quinacrine, was found to accumulate in rat and mouse pancreatic islet cells storing insulin, glucagon, pancreatic polypeptide, or somatostatin. Following administration of large doses of tolbutamide via an oro-gastric tube, the intensity of quinacrine fluorescence of insulin cells was substantially reduced. Similarly, the pancreatic insulin content was lowered. In contrast, the fluorescence intensity of the glucagon, pancreatic polypeptide and somatostatin cells appeared unaffected. Basal plasma insulin levels in the mouse were slightly elevated following quinacrine administration (25%). Glucose-stimulated insulin release was markedly enhanced (51%) in quinacrine-pretreated animals, whereas insulin release induced by cholinergic stimulation was unaffected. The results show that quinacrine accumulates in the various pancreatic islet cells. The drug seems to be confined to the secretory granules and affects the insulin response to glucose but not that to cholinergic stimulation, suggesting that these secretagogues act through different or partly different secretory pathways.