An insulinotropic effect of vitamin D analog with increasing intracellular Ca2+ concentration in pancreatic β-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 investigate 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 mVDR, dose-dependently augmented 16.7 mm glucose-induced insulin release from 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-dependent Ca2+ channels, nitrendipine. Moreover, both [Ca2+](i) elevation, caused by membrane depolarization, and sufficient intracellular glucose metabolism are required for the expression of these effects. 1 alpha,25(OH)(2)lumisterol(3), therefore, has a rapid insulinotropic effect, through nongenomic signal transduction via mVDR, that would be dependent on the augmentation of Ca2+ influx through voltage-dependent Ca2+ channels on the plasma membrane, being also linked to metabolic signals derived from glucose in pancreatic beta-cells. However, further investigations will be needed to discuss physiologically the meaning of insulinotropic effects of vitamin D through mVDR.