Abstract

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 1α,25(OH)2D3, but local production of 1α,25(OH)2D3, catalysed by the enzyme 25-hydroxyvitamin D3-1α-hydroxylase (1α-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 β cells) expressed 1α-OHase mRNA . The transcript in both cell types was similar to that seen in HKC-8 cells (a renal cell line, which expresses 1α-OHase). Western blot analysis and immunolocalisation identified 1α-OHase protein in MIN6 cells and human pancreatic tissue. In addition, suspensions of rat islets were able to convert 3H-25-hydroxyvitamin D3 to 3H-1α,25(OH)2D3, demonstrating 1α-OHase activity. Both cell systems expressed the Vitamin D receptor and 1α,25(OH)2D3 (50 nM) evoked a rapid rise in Ca2+i in MIN6 cells. This data clearly demonstrates islets are able to produce 1α,25(OH)2D3 and respond rapidly to treatment with 1α,25(OH)2D3. Therefore, we would postulate that local production of 1α,25(OH) 2D3 maybe an important autocrine link between Vitamin D status and pancreatic function. © 2004 Elsevier Ltd. All rights reserved.