Tmem27 is upregulated by vitamin D in INS-1 cells and its serum concentrations are low in patients with autoimmune diabetes

被引:7
作者
Pepaj, Milaim [1 ]
Gjerlaugsen, Nina [1 ]
Julien, Kari [1 ]
Thorsby, Per M. [1 ]
机构
[1] Oslo Univ Hosp, Dept Med Biochem, Hormone Lab, Oslo, Norway
关键词
Tmem27; Diabetes; pancreatic beta-cell; serum; vitamin D; EXPRESSION; COLLECTRIN; PROTEIN; ISLETS;
D O I
10.3109/00365513.2014.898322
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Transmembrane protein 27 (Tmem27), which is expressed in pancreatic beta-cells, plays an important role in insulin secretion and pancreatic beta-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)(2)D-3. Furthermore, we report that Tmem27 which is cleaved and released from, i.e. pancreatic beta-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.
引用
收藏
页码:358 / 365
页数:8
相关论文
共 17 条
[1]   Tmem27:: A cleaved and shed plasma membrane protein that stimulates pancreatic β cell proliferation [J].
Akpinar, P ;
Kuwajima, S ;
Krützfeldt, J ;
Stoffel, M .
CELL METABOLISM, 2005, 2 (06) :385-397
[2]   The role of transmembrane protein 27 (TMEM27) in islet physiology and its potential use as a beta cell mass biomarker [J].
Altirriba, J. ;
Gasa, R. ;
Casas, S. ;
Ramirez-Bajo, M. J. ;
Ros, S. ;
Gutierrez-Dalmau, A. ;
Ruiz de Villa, M. C. ;
Barbera, A. ;
Gomis, R. .
DIABETOLOGIA, 2010, 53 (07) :1406-1414
[3]   Expression of 25-hydroxyvitamin D3-1α-hydroxylase in pancreatic islets [J].
Bland, R ;
Markovic, D ;
Hills, CE ;
Hughes, SV ;
Chan, SLF ;
Squires, PE ;
Hewison, M .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2004, 89-90 (1-5) :121-125
[4]   The de novo synthesis of numerous proteins is decreased during vitamin D3 deficiency and is gradually restored by 1,25-dihydroxyvitamin D3 repletion in the islets of Langerhans of rats [J].
Bourlon, PM ;
Faure-Dussert, A ;
Billaudel, B .
JOURNAL OF ENDOCRINOLOGY, 1999, 162 (01) :101-109
[5]   Tmem27 dimerization, deglycosylation, plasma membrane depletion, and the extracellular Phe-Phe motif are negative regulators of cleavage by Bace2 [J].
Esterhazy, Daria ;
Akpinar, Pinar ;
Stoffel, Markus .
BIOLOGICAL CHEMISTRY, 2012, 393 (06) :473-484
[6]   Bace2 Is a β Cell-Enriched Protease that Regulates Pancreatic β Cell Function and Mass [J].
Esterhazy, Daria ;
Stuetzer, Ina ;
Wang, Haiyan ;
Rechsteiner, Markus P. ;
Beauchamp, Jeremy ;
Doebeli, Heinz ;
Hilpert, Hans ;
Matile, Hugues ;
Prummer, Michael ;
Schmidt, Alexander ;
Lieske, Nora ;
Boehm, Bernhard ;
Marselli, Lorella ;
Bosco, Domenico ;
Kerr-Conte, Julie ;
Aebersold, Ruedi ;
Spinas, Giatgen Andreia ;
Moch, Holger ;
Migliorini, Cristiano ;
Stoffel, Markus .
CELL METABOLISM, 2011, 14 (03) :365-377
[7]   The HNF-1 target Collectrin controls insulin exocytosis by SNARE complex formation [J].
Fukui, K ;
Yang, Q ;
Cao, Y ;
Takahashi, N ;
Hatakeyama, H ;
Wang, HY ;
Wada, J ;
Zhang, YL ;
Marselli, L ;
Nammo, T ;
Yoneda, K ;
Onishi, M ;
Higashiyama, S ;
Matsuzawa, Y ;
Gonzalez, FJ ;
Weir, GC ;
Kasai, H ;
Shimomura, L ;
Miyagawa, J ;
Wollheim, CB ;
Yamagata, K .
CELL METABOLISM, 2005, 2 (06) :373-384
[8]   1,25-dihydroxyvitamin D3 modulates expression of chemokines and cytokines in pancreatic islets: Implications for prevention of diabetes in nonobese diabetic mice [J].
Gysemans, CA ;
Cardozo, AK ;
Callewaert, H ;
Giulietti, A ;
Hulshagen, L ;
Bouillon, R ;
Eizirik, DL ;
Mathieu, C .
ENDOCRINOLOGY, 2005, 146 (04) :1956-1964
[9]   Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics [J].
Ong, SE ;
Blagoev, B ;
Kratchmarova, I ;
Kristensen, DB ;
Steen, H ;
Pandey, A ;
Mann, M .
MOLECULAR & CELLULAR PROTEOMICS, 2002, 1 (05) :376-386
[10]   Gene expression profiles for the human pancreas and purified islets in Type 1 diabetes: new findings at clinical onset and in long-standing diabetes [J].
Planas, R. ;
Carrillo, J. ;
Sanchez, A. ;
Ruiz de Villa, M. C. ;
Nunez, F. ;
Verdaguer, J. ;
James, R. F. L. ;
Pujol-Borrell, R. ;
Vives-Pi, M. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2010, 159 (01) :23-44