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

Abstract：

AIMS/HYPOTHESIS: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. METHODS: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. RESULTS: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 FXYD2gammaa was restricted to pancreatic islets and selectively detected in pancreatic beta cells. Analysis of human fetal pancreas samples showed the presence of FXYD2gammaa 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 FXYD2gammaa and loss of insulin-positive cells. CONCLUSIONS/INTERPRETATION:We propose human FXYD2gammaa as a novel beta cell-specific biomarker.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Flamez D,Roland I,Berton A,Kutlu B,Dufrane D,Beckers MC,De Waele E,Rooman I,Bouwens L,Clark A,Lonneux M,Jamar JF,Goldman S,Maréchal D,Goodman N,Gianello P,Van Huffel C,Salmon I,Eizirik DL

doi

10.1007/s00125-010-1714-z

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

1372-83

issue

eissn

0012-186X

issn

1432-0428

journal_volume

pub_type

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