GPR44 is a pancreatic protein restricted to the human beta cell
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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.
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 [3H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [3H]DTBZ.
GPR44 was available on the cell surface, and pancreatic RNA levels were restricted to the islets of Langerhans. [3H]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 [3H]AZD 3825 than for [3H]DTBZ.
GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.
KeywordsBeta cell imaging Beta cell mass GPR44 VMAT2
The study was supported by grants from JDRF, Diabetesfonden, Barndiabetesfonden, and Tore Nilssons Foundation for Medical Research. O.E.s position was supported by ExoDiab (Excellence of Diabetes Research in Sweden) and O.K.s position was supported by the National Institutes of Health (2U01AI065192-06).
Compliance with ethical standards
Conflict of interest
Paul Czernichow is an employee of EndoCells. The remaining authors report no conflicts of interest.
All work involving human tissue was conducted according to the principles expressed in the Declaration of Helsinki and in the European Council’s Convention on Human Rights and Biomedicine. Consent for organ donation (for clinical transplantation and for use in research) was obtained from the relatives of the deceased donors by the donor’s physicians and documented in the medical records of the deceased subject. The study was approved by the Regional Ethics Committee in Uppsala, Sweden (http://www.epn.se) according to the Act concerning the Ethical Review of Research Involving Humans (2003:460), Permit Number: Dnr 2009/371 (from April 10, 2013).
Human and animal rights disclosure
This article does not contain any studies with human or animal subjects performed by any of the authors.
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