title: Calcium insufficiency accelerates type 1 diabetes in vitamin D receptor-deficient nonobese diabetic (NOD) mice.
abstract: Vitamin D exerts important regulatory effects on the endocrine and immune systems. Autoimmune type 1 diabetes (T1D) development in the inbred NOD mouse strain can be accelerated by vitamin D insufficiency or suppressed by chronic treatment with high levels of 1α,25-dihydroxyvitamin D(3). Consequently, a report that T1D development was unaffected in NOD mice genetically 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 progeny rederived through embryo transfer. VDR-deficient NOD mice of both sexes showed significant acceleration of T1D. This acceleration was not associated with alterations in immune cells targeting pancreatic β-cells. Rather, the capacity of β-cells to produce and/or secrete insulin was severely impaired by the hypocalcaemia developing in VDR-deficient NOD mice fed a standard 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 β-cell insulin secretion, corrected glucose intolerance, and eliminated accelerated T1D in VDR-deficient NOD mice. These findings suggest that calcium and/or vitamin D supplementation may improve disease outcomes in some T1D-prone individuals that are calcium deficient.
authors.affiliation: The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Driver
authors.forename: Deanna J
authors.initials: DJ
authors.lastname: Lamont
authors.forename: Conny
authors.initials: C
authors.lastname: Gysemans
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: David V
authors.initials: DV
authors.lastname: Serreze
mesh_terms: D000818:Animals; D002118:Calcium / Q000172:deficiency* / Q000627:therapeutic use; D002136:Calcium, Dietary / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D006996:Hypocalcemia / Q000150:complications*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000172:deficiency* / Q000235:genetics; D014807:Vitamin D / Q000627:therapeutic use
chemical_list: D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D014807:Vitamin D; D002118:Calcium