Pedullà Marcella, Desiderio Vincenzo, Graziano Antonio, d'Aquino Riccardo, Puca Andrew, Papaccio Gianpaolo
Dipartimento di Pediatria, Seconda Università degli Studi di Napoli, Italy.
J Cell Biochem. 2007 Feb 15;100(3):808-14. doi: 10.1002/jcb.21095.
Non-hypercalcemic analogs of vitamin D(3) modulate the immune response through antigen-presenting cells (APCs) and activated T-cells. A large population-base case-control showed that vitamin D(3) intake significantly decreases the risk of type 1 diabetes development. The aim of this study was, therefore, to observe the in vivo effects of a vitamin D(3) analog administered to Bio Breeding (BB) rats. 1,25-Dihydroxy-16,23Z-diene-26,27-hexafluoro-19-nor vitamin D(3) (BXL-219, formerly Ro 26-2198) (BioXell, Milan, Italy) was administered in vivo to BB rats from days 42 to 110 of life at 0.2 microg/Kg BW. Control animals received only vehicle (olive oil, 4.8 microl/100 g BW). The animals of these two groups were subjected to insulin treatment as they became diabetic. Insulin (Humulin, 28.6 UI/day) was administered irrespective of diabetes occurrence to another group of rats for comparison. Blood glucose, insulin levels, glycosuria, degree of islet infiltration, and the expression of some antigens were observed. Results showed that the vitamin D(3) analog reduced diabetes incidence, although limitedly, in BB rats while administration of oral insulin increased diabetes incidence. In addition, the vitamin D(3) analog did not stimulate an enhancement in the expression of CD4 and CD25 in BB rats as it does in NOD mice, which may explain the failure of this as well as other antidiabetic treatments in the BB animal model of type 1 diabetes.
维生素D(3)的非高钙血症类似物通过抗原呈递细胞（APC）和活化的T细胞调节免疫反应。一项基于大量人群的病例对照研究表明，摄入维生素D(3)可显著降低1型糖尿病的发病风险。因此，本研究的目的是观察给生物繁殖（BB）大鼠施用维生素D(3)类似物的体内效果。在BB大鼠出生后第42天至110天，以0.2微克/千克体重的剂量给其体内施用1,25-二羟基-16,23Z-二烯-26,27-六氟-19-去甲维生素D(3)（BXL-219，原Ro 26-2198）（意大利米兰的BioXell公司）。对照动物仅接受赋形剂（橄榄油，4.8微升/100克体重）。这两组动物在患糖尿病时接受胰岛素治疗。另一组大鼠无论是否发生糖尿病均接受胰岛素（优泌林，28.6单位/天）治疗以作比较。观察血糖、胰岛素水平、糖尿、胰岛浸润程度以及一些抗原的表达。结果显示，维生素D(3)类似物虽有限地降低了BB大鼠的糖尿病发病率，而口服胰岛素的施用则增加了糖尿病发病率。此外，维生素D(3)类似物并未像在非肥胖糖尿病（NOD）小鼠中那样刺激BB大鼠CD4和CD25表达的增强，这可能解释了在1型糖尿病的BB动物模型中该治疗方法以及其他抗糖尿病治疗方法为何失败。
