Calcium Insufficiency Accelerates Type 1 Diabetes in Vitamin D Receptor-Deficient Nonobese Diabetic (NOD) Mice
Calcium Insufficiency Accelerates Type 1 Diabetes in Vitamin D Receptor-Deficient Nonobese Diabetic (NOD) Mice
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DOI：
10.1210/en.2011-1074
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发表时间：
2011-12-01
期刊：
影响因子：
4.8
通讯作者：
Serreze, David V.
中科院分区：
文献类型：
--
作者：
Driver, John P.;Lamont, Deanna J.;Serreze, David V.
维生素D对内分泌和免疫系统具有重要的调节作用。自身免疫性1型糖尿病（T1D）的发展可因维生素D不足而加速，或通过高水平的1 α，25-二羟基维生素D-3进行慢性治疗而抑制。因此，有报道称缺乏维生素D受体（VDR）的NOD小鼠的T1D发育不受影响，这是出乎意料的。为了进一步评估这一结果，将突变株引入杰克逊实验室，与NOD/ShiLtJ回交一次，并通过胚胎移植重新获得后代。两种性别的vdr缺陷NOD小鼠均表现出明显的T1D加速。这种加速与针对胰腺β细胞的免疫细胞的改变无关。相反，在饲喂标准啮齿动物食物的缺乏vdr的NOD小鼠中，β细胞产生和/或分泌胰岛素的能力受到低钙血症的严重损害。在VDR缺乏的NOD小鼠中，饲喂高乳糖钙拯救饮食，规避了VDR对肠道钙吸收的需求，使血清钙水平正常化，恢复β细胞胰岛素分泌，纠正葡萄糖耐受不良，并消除加速的T1D。这些发现表明，补充钙和/或维生素D可能改善一些缺钙的t1d易感个体的疾病结局。（内分泌学152:4620-4629,2011）
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 1 alpha,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 beta-cells. Rather, the capacity of beta-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 beta-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. (Endocrinology 152: 4620-4629, 2011)