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A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)γa as a pancreatic beta cell-specific biomarker

Daisy Flamez UGent, I Roland, A Berton, B Kutlu, D Dufrane, MC Beckers, E De Waele, I Rooman, L Bouwens, A Clark, et al. (2010) DIABETOLOGIA. 53(7). p.1372-1383
abstract
Non-invasive imaging of the pancreatic beta cell mass (BCM) requires the identification of novel and specific beta cell biomarkers. We have developed a systems biology approach to the identification of promising beta cell markers. We followed a functional genomics strategy based on massive parallel signal sequencing (MPSS) and microarray data obtained in human islets, purified primary rat beta cells, non-beta cells and INS-1E cells to identify promising beta cell markers. Candidate biomarkers were validated and screened using established human and macaque (Macacus cynomolgus) tissue microarrays. After a series of filtering steps, 12 beta cell-specific membrane proteins were identified. For four of the proteins we selected or produced antibodies targeting specifically the human proteins and their splice variants; all four candidates were confirmed as islet-specific in human pancreas. Two splice variants of FXYD domain containing ion transport regulator 2 (FXYD2), a regulating subunit of the Na+-K+-ATPase, were identified as preferentially present in human pancreatic islets. The presence of FXYD2 gamma a was restricted to pancreatic islets and selectively detected in pancreatic beta cells. Analysis of human fetal pancreas samples showed the presence of FXYD2 gamma a at an early stage (15 weeks). Histological examination of pancreatic sections from individuals with type 1 diabetes or sections from pancreases of streptozotocin-treated Macacus cynomolgus monkeys indicated a close correlation between loss of FXYD2 gamma a and loss of insulin-positive cells. We propose human FXYD2 gamma a as a novel beta cell-specific biomarker.
Please use this url to cite or link to this publication:
author
organization
alternative title
A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)gamma a as a pancreatic beta cell-specific biomarker
year
type
journalArticle (original)
publication status
published
subject
keyword
Pancreatic beta cells, CYTOKINE-INDUCED DYSFUNCTION, Imaging, Functional genomics, Diabetes, Beta cell biomarkers, DOUBLE-STRANDED-RNA, GENE-EXPRESSION, GAMMA-SUBUNIT, MASS, TYPE-1, APOPTOSIS, DEATH, PET, HYPOMAGNESEMIA
journal title
DIABETOLOGIA
Diabetologia
volume
53
issue
7
pages
1372 - 1383
Web of Science type
Article
Web of Science id
000278118700016
JCR category
ENDOCRINOLOGY & METABOLISM
JCR impact factor
6.973 (2010)
JCR rank
11/115 (2010)
JCR quartile
1 (2010)
ISSN
0012-186X
DOI
10.1007/s00125-010-1714-z
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
1072844
handle
http://hdl.handle.net/1854/LU-1072844
date created
2010-11-10 12:12:23
date last changed
2016-12-19 15:45:22
@article{1072844,
  abstract     = {Non-invasive imaging of the pancreatic beta cell mass (BCM) requires the identification of novel and specific beta cell biomarkers. We have developed a systems biology approach to the identification of promising beta cell markers.
We followed a functional genomics strategy based on massive parallel signal sequencing (MPSS) and microarray data obtained in human islets, purified primary rat beta cells, non-beta cells and INS-1E cells to identify promising beta cell markers. Candidate biomarkers were validated and screened using established human and macaque (Macacus cynomolgus) tissue microarrays.
After a series of filtering steps, 12 beta cell-specific membrane proteins were identified. For four of the proteins we selected or produced antibodies targeting specifically the human proteins and their splice variants; all four candidates were confirmed as islet-specific in human pancreas. Two splice variants of FXYD domain containing ion transport regulator 2 (FXYD2), a regulating subunit of the Na+-K+-ATPase, were identified as preferentially present in human pancreatic islets. The presence of FXYD2 gamma a was restricted to pancreatic islets and selectively detected in pancreatic beta cells. Analysis of human fetal pancreas samples showed the presence of FXYD2 gamma a at an early stage (15 weeks). Histological examination of pancreatic sections from individuals with type 1 diabetes or sections from pancreases of streptozotocin-treated Macacus cynomolgus monkeys indicated a close correlation between loss of FXYD2 gamma a and loss of insulin-positive cells.
We propose human FXYD2 gamma a as a novel beta cell-specific biomarker.},
  author       = {Flamez, Daisy and Roland, I and Berton, A and Kutlu, B and Dufrane, D and Beckers, MC and De Waele, E and Rooman, I and Bouwens, L and Clark, A and Lonneux, M and Jamar, JF and Goldman, S and Mar{\'e}chal, D and Goodman, N and Gianello, P and Van Huffel, C and Salmon, I and Eizirik, DL},
  issn         = {0012-186X},
  journal      = {DIABETOLOGIA},
  keyword      = {Pancreatic beta cells,CYTOKINE-INDUCED DYSFUNCTION,Imaging,Functional genomics,Diabetes,Beta cell biomarkers,DOUBLE-STRANDED-RNA,GENE-EXPRESSION,GAMMA-SUBUNIT,MASS,TYPE-1,APOPTOSIS,DEATH,PET,HYPOMAGNESEMIA},
  language     = {eng},
  number       = {7},
  pages        = {1372--1383},
  title        = {A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)\ensuremath{\gamma}a as a pancreatic beta cell-specific biomarker},
  url          = {http://dx.doi.org/10.1007/s00125-010-1714-z},
  volume       = {53},
  year         = {2010},
}

Chicago
Flamez, Daisy, I Roland, A Berton, B Kutlu, D Dufrane, MC Beckers, E De Waele, et al. 2010. “A Genomic-based Approach Identifies FXYD Domain Containing Ion Transport Regulator 2 (FXYD2)γa as a Pancreatic Beta Cell-specific Biomarker.” Diabetologia 53 (7): 1372–1383.
APA
Flamez, D., Roland, I., Berton, A., Kutlu, B., Dufrane, D., Beckers, M., De Waele, E., et al. (2010). A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)γa as a pancreatic beta cell-specific biomarker. DIABETOLOGIA, 53(7), 1372–1383.
Vancouver
1.
Flamez D, Roland I, Berton A, Kutlu B, Dufrane D, Beckers M, et al. A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)γa as a pancreatic beta cell-specific biomarker. DIABETOLOGIA. 2010;53(7):1372–83.
MLA
Flamez, Daisy, I Roland, A Berton, et al. “A Genomic-based Approach Identifies FXYD Domain Containing Ion Transport Regulator 2 (FXYD2)γa as a Pancreatic Beta Cell-specific Biomarker.” DIABETOLOGIA 53.7 (2010): 1372–1383. Print.