STIMULATORY EFFECT OF 1,25-DIHYDROXYVITAMIN-D(3) ON CALCIUM HANDLING AND INSULIN-SECRETION BY ISLETS FROM VITAMIN-D(3)-DEFICIENT RATS

Among the various vitamin D3 metabolites, 1,25-(OH)2D3 is the specific secosteroid hormone that can enhance, in vitro, the weak insulin resp onse to glucose of islets from vitamin D3-deficient rats. Because this potentiating effect is preceded by an increase in Ca2+ handling, seve ral putative sites of action were studied by measuring Ca-45(2+) and R b-86+ (as K+ tracer) efflux during perifusions in the presence of vari ous stimuli known to affect Ca2+ movements in different ways: high glu cose without calcium, high calcium without glucose, high potassium, or barium-theophylline without calcium or glucose. The present results s how that 1,25-(OH)2D3 may activate Ca2+ handling by at least two mecha nisms: (1) an increase of Ca2+ entry via voltage-dependent Ca2+ channe ls in the experiments in which extracellular Ca2+ was present and wher e Ca2+ channels were opened; this 1,25-(OH)2D3 influence on Ca2+ chann els was not mediated by a possible indirect influence on K+ channels b ecause Rb-86+ fluxes were never observed to be affected by the steroid ; (2) an enhancement of Ca-45(2+) mobilization from intracellular stor es as suggested by barium-theophylline stimulation and probably also v ia the Ca2+ stimulus. Both of these 1,25-(OH)2D3 influences tended to provide more calcium to the B cell of vitamin D3-deficient rats. But t his prerequisite was not sufficient in itself to potentiate the insuli n response; indeed, experiments with barium-theophylline suggested tha t 1,25-(OH)2D3 may also activate a cAMP-dependent exocytosis process.