Time course study of insulin secretion after 1,25-dihydroxyvitamin D3 administration.

Vitamin D3 is known to be involved in pancreatic endocrine function. The rapidity of action of the biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], was studied over time (from 0-72 h) on pancreatic insulin secretion by the subsequently isolated perfused pancreas of vitamin D-deficient rats pair-fed with vitamin D-deficient control rats treated with vehicle alone. At 8 h after 1,25(OH)2D3 administration (1.3 nmol), augmentation of the insulin secretion in response to 16.6 mM glucose had already significantly appeared and reached a maximum at 14 h, and then markedly decreased to pretreatment baseline values by 36 h. In a separate experiment using 20 mM arginine as a stimulus, insulin secretion from the isolated perfused pancreas also showed a significant increase at 8 h and demonstrated a maximum response at 14 h after 1,25(OH)2D3 administration, followed by gradual decrease to 72 h. The prevailing levels of serum parameters, including calcium, phosphorus, and glucose, seemed not to be involved in this mechanism, since these were not correlated to the amount of insulin secretion by the subsequently isolated perfused pancreas. Also the observed rapid effects of 1,25(OH)2D3 on insulin secretion appear not to be related to a rapid effect of the secosteroid on increased dietary/caloric intake. These results clearly establish both the dependence of and rapid dynamics response of the perfused pancreas to the potentiating effects of in vivo administered 1,25(OH)2D3 on either glucose- or arginine-mediated insulin secretion from the perfused pancreas.