Bjl. Billaudel et al., STIMULATORY EFFECT OF 1,25-DIHYDROXYVITAMIN-D(3) ON CALCIUM HANDLING AND INSULIN-SECRETION BY ISLETS FROM VITAMIN-D(3)-DEFICIENT RATS, Steroids, 58(7), 1993, pp. 335-341
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.