Unraveling the effects of 1,25(OH)(2)D-3 on global gene expression in pancreatic islets

Introduction: Vitamin D deficiency has been linked to type 1 and 2 diabetes, whereas supplementation may prevent both diseases. However, the extent of the effects of vitamin D or its metabolites directly on pancreatic islets is still largely unknown. The aim of the present study was to investigate how active vitamin D, 1,25(OH) 2D 3, affects beta cells directly by establishing its effects on global gene expression in healthy murine islets. Materials and methods: Pancreatic islets were isolated from 2 to 3 week old C57BL/6 mice and cultured in vitro with 1,25(OH) 2D 3 or vehicle for 6 and 24 h. Total RNA was extracted from the islets and the effects on global gene expression were analyzed using Affymetrix microarrays. Results and discussion: Exposure to 1,25(OH) 2D 3 compared to vehicle resulted in 306 and 151 differentially expressed genes after 6 and 24 h, respectively (n = 4,1.3-fold, p 0.02). Of these 220 were up-regulated, whereas 86 displayed a decreased expression after 6 h. Furthermore, expression levels were increased for 124 and decreased for 27 genes following 24 h of exposure. Formation of intercellular junctions, cytoskeletal organization, and intracellular trafficking as well as lipid metabolism and ion transport were among the most affected gene classes. Effects on several genes already identified as being part of vitamin D signaling in other cell types were observed along with genes known to affect insulin release, although with our assay we were not able to detect any effects of 1,25(OH) 2D 3 on glucose-stimulated insulin release from healthy pancreatic islets. Conclusion: The effects of 1,25(OH) 2D 3 on the expression of cytoskeletal and intracellular trafficking genes along with genes involved in ion transport may influence insulin exocytosis. However, an effect of 1,25(OH) 2D 3 on insulin release could not be detected for healthy islets in contrast to islets subjected to pathological conditions such as cytokine exposure and vitamin D deficiency as suggested by other studies. Thus, in addition to previously identified tolerogenic effects on the immune system, 1,25(OH) 2D 3 may affect basic functions of pancreatic beta cells, with the potential to render them more resistant to the detrimental conditions encountered during type 1 and 2 diabetes.