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Early differences in islets from prediabetic NOD mice : combined microarray and proteomic analysis

Inne Crèvecoeur, Valborg Gudmundsdottir, Saurabh Vig, Fernanda Marques Câmara Sodré, Wannes D’Hertog, Ana Carolina Elisa Fierro Gutierrez, Leentje Van Lommel, Conny Gysemans, Kathleen Marchal UGent, Etienne Waelkens, et al. (2017) DIABETOLOGIA. 60(3). p.475-489
abstract
AIMS/HYPOTHESIS: Type 1 diabetes is an endocrine disease where a long preclinical phase, characterised by immune cell infiltration in the islets of Langerhans, precedes elevated blood glucose levels and disease onset. Although several studies have investigated the role of the immune system in this process of insulitis, the importance of the beta cells themselves in the initiation of type 1 diabetes is less well understood. The aim of this study was to investigate intrinsic differences present in the islets from diabetes-prone NOD mice before the onset of insulitis. METHODS: The islet transcriptome and proteome of 2-3-week-old mice was investigated by microarray and 2-dimensional difference gel electrophoresis (2D-DIGE), respectively. Subsequent analyses using sophisticated pathway analysis and ranking of differentially expressed genes and proteins based on their relevance in type 1 diabetes were performed. RESULTS: In the preinsulitic period, alterations in general pathways related to metabolism and cell communication were already present. Additionally, our analyses pointed to an important role for post-translational modifications (PTMs), especially citrullination by PAD2 and protein misfolding due to low expression levels of protein disulphide isomerases (PDIA3, 4 and 6), as causative mechanisms that induce beta cell stress and potential auto-antigen generation. CONCLUSIONS/INTERPRETATION: We conclude that the pancreatic islets, irrespective of immune differences, may contribute to the initiation of the autoimmune process. DATA AVAILABILITY: All microarray data are available in the ArrayExpress database ( www.ebi.ac.uk/arrayexpress ) under accession number E-MTAB-5264.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
IBCN, 2D-DIGE, Beta cells, Intrinsic differences, Microarray, NOD mice, Pathway analysis, Post-translational modifications, Type 1 diabetes, REGULATES INSULIN-SECRETION, PANCREATIC BETA-CELLS, DATA INTEGRATION, GENE, MOUSE, SUSCEPTIBILITY, AUTOANTIGENS, EXPRESSION, RESISTANCE, EVOLUTION
journal title
DIABETOLOGIA
Diabetologia
volume
60
issue
3
pages
475 - 489
Web of Science type
Article
Web of Science id
000394462100013
ISSN
0012-186X
DOI
10.1007/s00125-016-4191-1
project
Bioinformatics: from nucleotids to networks (N2N)
language
English
UGent publication?
yes
classification
A1
additional info
the last two authors contributed equally to this work
copyright statement
I have transferred the copyright for this publication to the publisher
id
8510460
handle
http://hdl.handle.net/1854/LU-8510460
date created
2017-02-20 18:37:25
date last changed
2017-04-25 07:25:29
@article{8510460,
  abstract     = {AIMS/HYPOTHESIS: Type 1 diabetes is an endocrine disease where a long preclinical phase, characterised by immune cell infiltration in the islets of Langerhans, precedes elevated blood glucose levels and disease onset. Although several studies have investigated the role of the immune system in this process of insulitis, the importance of the beta cells themselves in the initiation of type 1 diabetes is less well understood. The aim of this study was to investigate intrinsic differences present in the islets from diabetes-prone NOD mice before the onset of insulitis.
METHODS: The islet transcriptome and proteome of 2-3-week-old mice was investigated by microarray and 2-dimensional difference gel electrophoresis (2D-DIGE), respectively. Subsequent analyses using sophisticated pathway analysis and ranking of differentially expressed genes and proteins based on their relevance in type 1 diabetes were performed.
RESULTS: In the preinsulitic period, alterations in general pathways related to metabolism and cell communication were already present. Additionally, our analyses pointed to an important role for post-translational modifications (PTMs), especially citrullination by PAD2 and protein misfolding due to low expression levels of protein disulphide isomerases (PDIA3, 4 and 6), as causative mechanisms that induce beta cell stress and potential auto-antigen generation.
CONCLUSIONS/INTERPRETATION: We conclude that the pancreatic islets, irrespective of immune differences, may contribute to the initiation of the autoimmune process.
DATA AVAILABILITY: All microarray data are available in the ArrayExpress database ( www.ebi.ac.uk/arrayexpress ) under accession number E-MTAB-5264.},
  author       = {Cr{\`e}vecoeur, Inne and Gudmundsdottir, Valborg and Vig, Saurabh and Marques C{\^a}mara Sodr{\'e}, Fernanda and D{\textquoteright}Hertog, Wannes and Fierro Gutierrez, Ana Carolina Elisa and Van Lommel, Leentje and Gysemans, Conny and Marchal, Kathleen and Waelkens, Etienne and Schuit, Frans and Brunak, S{\o}ren and Overbergh, Lut and Mathieu, Chantal},
  issn         = {0012-186X},
  journal      = {DIABETOLOGIA},
  keyword      = {IBCN,2D-DIGE,Beta cells,Intrinsic differences,Microarray,NOD mice,Pathway analysis,Post-translational modifications,Type 1 diabetes,REGULATES INSULIN-SECRETION,PANCREATIC BETA-CELLS,DATA INTEGRATION,GENE,MOUSE,SUSCEPTIBILITY,AUTOANTIGENS,EXPRESSION,RESISTANCE,EVOLUTION},
  language     = {eng},
  number       = {3},
  pages        = {475--489},
  title        = {Early differences in islets from prediabetic NOD mice : combined microarray and proteomic analysis},
  url          = {http://dx.doi.org/10.1007/s00125-016-4191-1},
  volume       = {60},
  year         = {2017},
}

Chicago
Crèvecoeur, Inne, Valborg Gudmundsdottir, Saurabh Vig, Fernanda Marques Câmara Sodré, Wannes D’Hertog, Ana Carolina Elisa Fierro Gutierrez, Leentje Van Lommel, et al. 2017. “Early Differences in Islets from Prediabetic NOD Mice : Combined Microarray and Proteomic Analysis.” Diabetologia 60 (3): 475–489.
APA
Crèvecoeur, I., Gudmundsdottir, V., Vig, S., Marques Câmara Sodré, F., D’Hertog, W., Fierro Gutierrez, A. C. E., Van Lommel, L., et al. (2017). Early differences in islets from prediabetic NOD mice : combined microarray and proteomic analysis. DIABETOLOGIA, 60(3), 475–489.
Vancouver
1.
Crèvecoeur I, Gudmundsdottir V, Vig S, Marques Câmara Sodré F, D’Hertog W, Fierro Gutierrez ACE, et al. Early differences in islets from prediabetic NOD mice : combined microarray and proteomic analysis. DIABETOLOGIA. 2017;60(3):475–89.
MLA
Crèvecoeur, Inne, Valborg Gudmundsdottir, Saurabh Vig, et al. “Early Differences in Islets from Prediabetic NOD Mice : Combined Microarray and Proteomic Analysis.” DIABETOLOGIA 60.3 (2017): 475–489. Print.