title: GPR44 is a pancreatic protein restricted to the human beta cell.
abstract: OBJECTIVE
  To address questions regarding onset and progression of types 1 and 2 diabetes (T1D/T2D), surrogate imaging biomarkers for beta cell function and mass are needed. Here, we assess the potential of GPR44 as a surrogate marker for beta cells, in a direct comparison with clinically used biomarker VMAT2.
  
  
  METHODS
  GPR44 surface availability was assessed by flow cytometry of human beta cells. RNA transcription levels in different pancreas compartments were evaluated. The density of GPR44 receptor in endocrine and exocrine tissues was assessed by the radiolabeled GPR44 ligand [(3)H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [(3)H]DTBZ.
  
  
  RESULTS
  GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [(3)H]AZD 3825 had nanomolar affinity for GPR44 in human islets and EndoC-βH1 beta cells, and the specific binding to human beta cells was close to 50 times higher than in exocrine preparations. The endocrine-to-exocrine binding ratio was approximately 10 times higher for [(3)H]AZD 3825 than for [(3)H]DTBZ.
  
  
  CONCLUSIONS
  GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, 751 83, Uppsala, Sweden.
authors.forename: Ewa
authors.initials: E
authors.lastname: Hellström-Lindahl
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, 751 83, Uppsala, Sweden.|Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, 751 85, Uppsala, Sweden.
authors.forename: Angelika
authors.initials: A
authors.lastname: Danielsson
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, 751 83, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ponten
authors.affiliation: Endocells, 216 BD Saint Germain, 75007, Paris, France.
authors.forename: Paul
authors.initials: P
authors.lastname: Czernichow
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, 751 83, Uppsala, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Korsgren
authors.affiliation: Department of Radiology, Oncology and Radiation Sciences, Uppsala University, 751 83, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Johansson
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, 751 83, Uppsala, Sweden. olof.eriksson@pet.medchem.uu.se.
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D003920:Diabetes Mellitus / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D009928:Organ Specificity; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000235:genetics / Q000378:metabolism*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; C036293:prostaglandin D2 receptor
keywords: Beta cell imaging; Beta cell mass; GPR44; VMAT2