Bland Rosemary, Markovic Danijela, Hills Claire E, Hughes Susan V, Chan Susan L F, Squires Paul E, Hewison Martin
Department of Biological Sciences, Biomedical Research Institute, The University of Warwick, Coventry CV4 7AL, UK.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):121-5. doi: 10.1016/j.jsbmb.2004.03.115.
A number of studies have suggested that Vitamin D has a potential role in the development/treatment of diabetes. These effects may be mediated by circulating levels of 1alpha,25(OH)(2)D(3), but local production of 1alpha,25(OH)(2)D(3), catalysed by the enzyme 25-hydroxyvitamin D(3)-1alpha-hydroxylase (1alpha-OHase), is also likely to be important. RT-PCR analyses demonstrated that both isolated rat islets and MIN6 cells (mouse insulin-secreting cell line, characteristic of beta cells) expressed 1alpha-OHase mRNA. The transcript in both cell types was similar to that seen in HKC-8 cells (a renal cell line, which expresses 1alpha-OHase). Western blot analysis and immunolocalisation identified 1alpha-OHase protein in MIN6 cells and human pancreatic tissue. In addition, suspensions of rat islets were able to convert [3H]-25-hydroxyvitamin D(3) to [3H]-1alpha,25(OH)(2)D(3), demonstrating 1alpha-OHase activity. Both cell systems expressed the Vitamin D receptor and 1alpha,25(OH)(2)D(3) (50nM) evoked a rapid rise in Ca(2+) in MIN6 cells. This data clearly demonstrates islets are able to produce 1alpha,25(OH)(2)D(3) and respond rapidly to treatment with 1alpha,25(OH)(2)D(3). Therefore, we would postulate that local production of 1alpha,25(OH)(2)D(3) maybe an important autocrine link between Vitamin D status and pancreatic function.
多项研究表明，维生素D在糖尿病的发生发展/治疗中可能发挥作用。这些作用可能是由循环中的1α,25(OH)₂D₃水平介导的，但由25-羟维生素D₃-1α-羟化酶（1α-OHase）催化的局部1α,25(OH)₂D₃生成也可能很重要。逆转录聚合酶链反应（RT-PCR）分析表明，分离的大鼠胰岛和MIN6细胞（小鼠胰岛素分泌细胞系，具有β细胞特征）均表达1α-OHase mRNA。两种细胞类型中的转录本与HKC-8细胞（一种表达1α-OHase的肾细胞系）中的相似。蛋白质免疫印迹分析和免疫定位鉴定出MIN6细胞和人胰腺组织中有1α-OHase蛋白。此外，大鼠胰岛悬液能够将[³H]-25-羟维生素D₃转化为[³H]-1α,25(OH)₂D₃，证明有1α-OHase活性。两种细胞系统均表达维生素D受体，并且1α,25(OH)₂D₃（50nM）可引起MIN6细胞中[Ca²⁺]i迅速升高。这些数据清楚地表明胰岛能够产生1α,25(OH)₂D₃并对1α,25(OH)₂D₃治疗迅速做出反应。因此，我们推测1α,25(OH)₂D₃的局部生成可能是维生素D状态与胰腺功能之间重要的自分泌联系。
