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

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Flamez, D. Roland, I. Berton, A. Kutlu, B. Dufrane, Denis [UCL] De Waele, Eric [UCL] Lonneux, Max [UCL] Jamar, J. F. [UCL] Gianello, Pierre [UCL]

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.

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Bibliographic reference Flamez, D. ; Roland, I. ; Berton, A. ; Kutlu, B. ; Dufrane, Denis ; et. al. A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)gamma a as a pancreatic beta cell-specific biomarker. In: Diabetologia : clinical and experimental diabetes and metabolism, Vol. 53, no. 7, p. 1372-1383 (2010)
Permanent URL http://hdl.handle.net/2078.1/34413