The risk alleles of the TCF7L2 gene (rs12255372 and rs7903146) were strongly associated with type 2 diabetes, even after controlling for traditional risk factors in both a cross-sectional and prospective setting. These risk alleles were associated with indices of reduced beta-cell function.

Background Vitamin D affects the pancreatic beta cell function and in vitro studies have shown that vitamin D may influence insulin secretion, apoptosis, and gene regulation. However, the outcomes have differed and there has been uncertainty regarding the effect of different vitamin D metabolites on insulin secretion. Objectives We hypothesized that vitamin D could increase insulin secretion in insulin producing beta cells and investigated the effect of 25(OH) vitamin D and 1,25(OH) 2 vitamin D on insulin secretion. Methods The study was conducted in INS1E cells, an established insulinoma cell line from rat. The cells were divided into three groups; a control group, a group with 1,25(OH) 2 vitamin D enriched medium (10 nM), and a group with 25(OH) vitamin D (10 nM) supplemented medium. After 72 hours of treatment, the cells underwent glucose stimulation at different concentrations (0, 5, 11, and 22 mM) for 60 minutes. Results INS1E cells treated with 1,25(OH) 2 vitamin D showed a trend towards increased insulin secretion at all glucose concentrations compared to control cells and at 22 mM glucose, the difference was significant (18.40 +/- 1.97 vs 12.90 +/- 2.22 nmol/L, P < 0.05). However, pretreatment with 25(OH) vitamin D did not show any significant increase in insulin secretion compared to cells without vitamin D treatment. There was no difference in insulin secretion in cells not stimulated with glucose. Conclusions Treatment with 1,25(OH) 2 vitamin D combined with high levels of glucose increased insulin secretion in INS1E cells, whereas 25(OH) vitamin D had no effect. This suggests that glucose stimulated insulin secretion in INS1E beta cells appears to be related to the type of vitamin D metabolite treatment.

Together, we reveal a number of novel vitamin D-regulated proteins that may contribute to a better understanding of the reported beneficial effects of vitamin D on pancreatic β-cells. Copyright © 2016 John Wiley & Sons, Ltd.

In this study, we discovered a number of novel 1,25-(OH)2 D3 -regulated proteins, which may contribute to a better understanding of the reported beneficial effects of vitamin D on pancreatic β-cells. All in all, our findings should pave the way for future studies providing insights into molecular mechanisms by which 1,25-(OH)2 D3 regulates protein expression in pancreatic β-cells.

Transmembrane protein 27 (Tmem27), which is expressed in pancreatic β-cells, plays an important role in insulin secretion and pancreatic β-cell proliferation. Analysis of the INS-1 cell proteome using stable isotope labeling by amino acids in cell culture (SILAC) in combination with LC-MS identified Tmem27 as the one of most robustly (up to seven-fold) upregulated proteins after treatment with the active metabolite of vitamin D, 1,25-(OH)2D3. Furthermore, we report that Tmem27 which is cleaved and released from, i.e. pancreatic β-cells, is present in human serum and its levels are significantly lower in subjects with autoimmune diabetes as compared to healthy individuals (13% of the levels). Additionally, Tmem27 correlated positively (0.70) with C-peptide serum levels in healthy subjects. Our data indicate that Tmem27 could be of potential value as a serum marker for the pathogenesis of diabetes and as such may warrant the development of measurement methods with lower limit of detection for its further validation.

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