Vitamin D Rescues Pancreatic β Cell Dysfunction due to Iron Overload via Elevation of the Vitamin D Receptor and Maintenance of Ca Homeostasis. Molecular nutrition & food research SCOPE:Accumulating evidence indicates that micronutrients are related to metabolic diseases. However, comparatively less attention has been devoted to their influence on each other during the development of metabolic diseases. To investigate the underlying mechanisms, the effects of iron and vitamin D on pancreatic β cell functions are examined. METHODS AND RESULTS:Iron overload is induced in INS-1 rat insulinoma pancreatic β cells and it is found that iron overload dramatically reduce expression of the vitamin D receptor (VDR). Iron overload-induced β cell dysfunction is rescued by 1,25-dihydroxyvitamin D (1,25(OH) D ) cotreatment via restoration of VDR level and the consequent maintenance of Ca homeostasis. Iron accumulation is also observed in the islets of 22-month-old C57BL/6 mice fed with a chow diet (1000 IU vitamin D per kg). In contrast, islet iron accumulation and hyperinsulinemia are ameliorated in mice fed with a vitamin D -supplemented diet (20 000 IU kg ). CONCLUSION:The authors show that functional failure of β cells due to iron accumulation is rescued by 1,25(OH) D , and iron overload significantly reduces VDR levels in β cells. These results suggest that iron and vitamin D inversely influence pancreatic β cell function. 10.1002/mnfr.202000772