Vitamin D3 treatment can improve within 3 days the low insulin secretion of vitamin D3-deficient rats. One of its metabolite active in vivo, 1,25(OH)2D3 cannot stimulate the insulin secretion in vitro within 2 h, except when islets came from 24 h-vitamin D3 prepared rats. These findings led us to determine the respective in vitro activity of three vitamin D3 metabolites [1,25(OH)2D3; 24,25(OH)2D3 and 25(OH)D3] on cellular events in perifused islets derived from vitamin D3-deficient rats which were injected with vitamin D3 24 h earlier. Three experimental conditions were studied: either a rise in metabolite concentration during a steady-state 8.3 mmol/l glucose medium, or without glucose, or a rise in glucose concentration (16.7 mmol/l) during a steady-state vitamin D3 metabolite concentration. The 1,25(OH)2D3 was the only of the 3 metabolites active both on insulin release and 45Ca2+ efflux. None of the three metabolites modified K+ fluxes (86Rb as a tracer). The in vitro specific stimulatory action of 1,25(OH)2D3 on B cell was rapidly seen within a few minutes, and occurred only in the presence of glucose stimulation. These results suggest that 1,25(OH)2D3 might potentiate the insulin response to glucose by an action on Ca2+ handling, either by enhancing Ca2+ entry in the B cell and/or Ca2+ mobilization from intracellular organelles.
Animals Calcitriol