title: A genomic-based approach identifies FXYD domain containing ion transport regulator 2 (FXYD2)gammaa as a pancreatic beta cell-specific biomarker.
abstract: OBJECTIVE
  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
  We propose human FXYD2gammaa as a novel beta cell-specific biomarker.
authors.affiliation: Laboratory of Experimental Medicine, Université Libre de Bruxelles, Route de Lennik 808, 1070, Brussels, Belgium. Daisy.Flamez@UGent.be
authors.forename: D
authors.initials: D
authors.lastname: Flamez
authors.forename: I
authors.initials: I
authors.lastname: Roland
authors.forename: A
authors.initials: A
authors.lastname: Berton
authors.forename: B
authors.initials: B
authors.lastname: Kutlu
authors.forename: D
authors.initials: D
authors.lastname: Dufrane
authors.forename: M C
authors.initials: MC
authors.lastname: Beckers
authors.forename: E
authors.initials: E
authors.lastname: De Waele
authors.forename: I
authors.initials: I
authors.lastname: Rooman
authors.forename: L
authors.initials: L
authors.lastname: Bouwens
authors.forename: A
authors.initials: A
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Lonneux
authors.forename: J F
authors.initials: JF
authors.lastname: Jamar
authors.forename: S
authors.initials: S
authors.lastname: Goldman
authors.forename: D
authors.initials: D
authors.lastname: Maréchal
authors.forename: N
authors.initials: N
authors.lastname: Goodman
authors.forename: P
authors.initials: P
authors.lastname: Gianello
authors.forename: C
authors.initials: C
authors.lastname: Van Huffel
authors.forename: I
authors.initials: I
authors.lastname: Salmon
authors.forename: D L
authors.initials: DL
authors.lastname: Eizirik
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D023281:Genomics / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D008251:Macaca / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D046888:Tissue Array Analysis
chemical_list: D015415:Biomarkers; C416502:FXYD2 protein, human; D000254:Sodium-Potassium-Exchanging ATPase