Vitamin D exerts important regulatory effects on the endocrine and immune systems. Autoimmune type 1 diabetes (T1D) de- velopment in the inbred NOD mouse strain can be accelerated by vitamin D insufficiency or suppressed by chronic treatment with high levels of 1a,25-dihydroxyvitamin D3. Consequently, a re- port that T1D development was unaffected in NOD mice genet- ically lacking the vitamin D receptor (VDR) was unexpected. To further assess this result, the mutant stock was imported to The Jackson Laboratory, backcrossed once to NOD/ShiLtJ, and prog- eny rederived through embryo transfer. VDR-deficient NOD mice of both sexes showed significant acceleration of T1D. This ac- celeration was not associated with alterations in immune cells targeting pancreatic B-cells. Rather, the capacity of B-cells to produce and/or secrete insulin was severely impaired by the hy- pocalcaemia developing in VDR-deficient NOD mice fed a stan- dard rodent chow diet. Feeding a high-lactose calcium rescue diet that circumvents a VDR requirement for calcium absorption from the intestine normalized serum calcium levels, restored B-cell insulin secretion, corrected glucose intolerance, and elim- inated accelerated T1D in VDR-deficient NOD mice. These find- ings suggest that calcium and/or vitamin D supplementation may improve disease outcomes in some T1D-prone individuals that are calcium deficient.
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