Stimulatory effect of 1,25-dihydroxyvitamin D3 on calcium handling and insulin secretion by islets from vitamin D3-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 response to glucose of islets from vitamin D3-deficient rats. Because this potentiating effect is preceded by an increase in Ca2+ handling, several putative sites of action were studied by measuring 45Ca2+ and 86Rb+ (as K+ tracer) efflux during perifusions in the presence of various stimuli known to affect Ca2+ movements in different ways: high glucose without calcium, high calcium without glucose, high potassium, or barium-theophylline without calcium or glucose. The present results show that 1,25-(OH)2D3 may activate Ca2+ handling by at least two mechanisms: (1) an increase of Ca2+ entry via voltage-dependent Ca2+ channels in the experiments in which extracellular Ca2+ was present and where Ca2+ channels were opened; this 1,25-(OH)2D3 influence on Ca2+ channels was not mediated by a possible indirect influence on K+ channels because 86Rb+ fluxes were never observed to be affected by the steroid; (2) an enhancement of 45Ca2+ mobilization from intracellular stores as suggested by barium-theophylline stimulation and probably also via 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 this prerequisite was not sufficient in itself to potentiate the insulin response; indeed, experiments with barium-theophylline suggested that 1,25-(OH)2D3 may also activate a cAMP-dependent exocytosis process.
Billaudel
B J
BJ
Laboratoire d'Endocrinologie, UFR de Biologie, Université Bordeaux I, Talence, France.
Delbancut
A P
AP
Sutter
B C
BC
Faure
A G
AG
D000818:Animals; D001464:Barium / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002412:Cations; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013806:Theophylline / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000503:physiopathology*
D002412:Cations; D007328:Insulin; D001464:Barium; D013806:Theophylline; D002117:Calcitriol; D005947:Glucose; D011188:Potassium; D002118:Calcium