Discovery of novel vitamin D‐regulated proteins in INS‐1 cells: a proteomic approach. Issue 5 (6th February 2015)

• Record Type: Journal Article
• Authors: Pepaj, Milaim; Bredahl, May K.; Gjerlaugsen, Nina; Bornstedt, Mette E.; Thorsby, Per M.
• Is Part Of: Diabetes/metabolism research and reviews. Volume 31:Issue 5(2015:Jul.)
• Page Start: 481
• Page End: 491
• Publication Date: 2015-02-06
• Subjects: Diabetes -- Periodicals; Metabolism -- Periodicals; 616.642
• DOI: 10.1002/dmrr.2629
• Languages: English
• ISSNs: 1520-7552

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="dmrr2629-sec-0001" sec-type="section"> <title>Background</title> <p>Experimental evidence indicates that vitamin D may have a beneficial role in pancreatic <italic>β</italic>‐cell function. Global gene expression studies have shown that the active metabolite 1, 25‐dihydroxyvitamin D<sub>3</sub> [1, 25‐(OH)<sub>2</sub>D<sub>3</sub>] modulates genes involved in ion transport, lipid metabolism and insulin secretion.</p> </sec> <sec id="dmrr2629-sec-0002" sec-type="section"> <title>Methods</title> <p>We employed stable isotope labelling by amino acids in cell culture in combination with liquid chromatography–tandem mass spectrometry to quantitatively assess the impact of two vitamin D metabolites, 1, 25‐(OH)<sub>2</sub>D<sub>3</sub> and 25‐hydroxyvitamin D<sub>3</sub> [25‐(OH)D<sub>3</sub>], on global protein expression on a model rat <italic>β</italic>‐cell line, insulinoma‐derived INS‐1 cells.</p> </sec> <sec id="dmrr2629-sec-0003" sec-type="section"> <title>Results</title> <p>Although treatment with 1, 25‐(OH)<sub>2</sub>D<sub>3</sub> resulted in 31 differentially expressed proteins, 25‐(OH)D<sub>3</sub> had no impact on protein expression. Of these 31 proteins, 29 were upregulated, whereas two showed a decrease in abundance. Proteins whose expression levels markedly increased in the presence of 1, 25‐(OH)<sub>2</sub>D<sub>3</sub> included Crat, Hmgn2, Protein Tmsbl1 and Gdap1. One of the most important findings in this study is upregulation of proteins implicated in insulin granule motility and insulin exocytosis, suggesting a positive effect on insulin secretion. Moreover, modulation of several membrane transport proteins suggests that 1, 25‐(OH)<sub>2</sub>D<sub>3</sub> has an impact on the homeostatic regulation of ions, which is critical for most functions in the <italic>β</italic>‐cell.</p> </sec> <sec id="dmrr2629-sec-0004" sec-type="section"> <title>Conclusions</title> <p>In this study, we discovered a number of novel 1, 25‐(OH)<sub>2</sub>D<sub>3</sub>‐regulated proteins, which may contribute to a better understanding of the reported beneficial effects of vitamin D on pancreatic <italic>β</italic>‐cells. All in all, our findings should pave the way for future studies providing insights into molecular mechanisms by which 1, 25‐(OH)<sub>2</sub>D<sub>3</sub> regulates protein expression in pancreatic <italic>β</italic>‐cells. Copyright © 2014 John Wiley & Sons, Ltd.</p> </sec> </abstract>