An insulinotropic effect of vitamin D analog with increasing intracellularCa2+ concentration in pancreatic beta-cells through nongenomic signal transduction

The effect of 1 alpha,25-dihydroxylumisterol, (1 alpha,25(OH)(2)lumisterol( 3)) on insulin release from rat pancreatic beta-cells was measured to inves tigate the nongenomic action of vitamin D via the putative membrane vitamin D receptor (mVDR). 1 alpha,25(OH)(2)lumisterol(3), a specific agonist of m VDR, dose-dependently augmented 16.7 mm glucose-induced insulin release fro m rat pancreatic islets and increased the intracellular Ca2+ concentration ([Ca2+](i)), though not increasing Ca2+ efficacy in the exocytotic system. These effects were completely abolished by an antagonist of mVDR, 1 beta,25 -dihydroxyvitamin D-3 (1 beta,25(OH)(2)D-3), or by a blocker of voltage-dep endent Ca2+ channels, nitrendipine. Moreover, both [Ca2+](i) elevation, cau sed by membrane depolarization, and sufficient intracellular glucose metabo lism are required for the expression of these effects. 1 alpha,25(OH)(2)lum isterol(3), therefore, has a rapid insulinotropic effect, through nongenomi c signal transduction via mVDR, that would be dependent on the augmentation of Ca2+ influx through voltage-dependent Ca2+ channels on the plasma membr ane, being also linked to metabolic signals derived from glucose in pancrea tic beta-cells. However, further investigations will be needed to discuss p hysiologically the meaning of insulinotropic effects of vitamin D through m VDR.