Proteomic analysis of the INS-1E secretome identify novel vitamin D-regulated proteins

• Published in: Diabetes/metabolism research and reviews 2016-09, Vol.32 (6), p.514-521
• Main Authors: Pepaj, Milaim, Bredahl, May K., Gjerlaugsen, Nina, Thorsby, Per M.
• Format: Article
• Language: English
• Subjects: 1,25‐dihydroxyvitamin D3; 25-dihydroxyvitamin D3; Animals; Biomarkers - metabolism; Calcitriol - pharmacology; Cell growth; Gene Expression Regulation - drug effects; INS-1E; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Insulinoma - drug therapy; Insulinoma - metabolism; Insulinoma - pathology; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Proteins; Proteome - analysis; proteomics; Proteomics - methods; Rats; secretome; SILAC; Tumor Cells, Cultured; Vitamin D
• ISSN: 1520-7552; 1520-7560
• DOI: 10.1002/dmrr.2777

Background Experimental evidence indicates that vitamin D may have a beneficial role in pancreatic β‐cell function. Methods In the present study, stable isotope labelling by amino acids in cell culture (SILAC) in combination with liquid chromatography–tandem mass spectrometry was used to quantitatively assess the impact of the active vitamin D metabolite, 1,25‐(OH)2D3, on global protein expression in INS‐1E cell secretome. Results Twenty‐one proteins were found up‐regulated (≥1.5 fold changes) and three down‐regulated (≤0.67) after treatment of INS‐1E cells with 1,25‐(OH)2D3. Up‐regulation of proteins implicated in β‐cell growth and proliferation, such as IGF2, IGFBP7 and gelsolin, suggest that 1,25‐(OH)2D3 has a positive effect on β‐cell growth and proliferation. Moreover, modulations of several proteins implicated in prohormone processing and insulin exocytosis (IGF2, IGFBP7, Scg5, ProSAAS, Fabp5, Ptprn2 and gelsolin) appear to support the hypothesis that 1,25‐(OH)2D3 plays positive modulatory role in insulin processing and secretion. Conclusions 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.