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Acta Diabetologica

, Volume 53, Issue 3, pp 413–421 | Cite as

GPR44 is a pancreatic protein restricted to the human beta cell

  • Ewa Hellström-Lindahl
  • Angelika Danielsson
  • Fredrik Ponten
  • Paul Czernichow
  • Olle Korsgren
  • Lars Johansson
  • Olof Eriksson
Original Article

Abstract

Aims

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 [3H]AZD 3825. A direct comparison with the established beta cell marker VMAT2 was performed by radiolabeled [3H]DTBZ.

Results

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.

Conclusion

GPR44 is a highly beta cell-specific target, which potentially offers improved imaging contrast between the human beta cell and the exocrine pancreas.

Keywords

Beta cell imaging Beta cell mass GPR44 VMAT2 

Notes

Acknowledgments

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.

Ethical standard

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.

Informed consent

None.

Supplementary material

592_2015_811_MOESM1_ESM.pdf (55 kb)
Supplementary Fig. 1. Representative saturation binding experiments to assess affinity (Kd) and receptor density (Bmax) of [3H]AZD 3825 (A-C) and [3H]DTBZ (D-E). Homogenized human pancreatic endocrine (A, D) or exocrine (B, E) preparations was used. [3H]AZD 3825 binding to pure human beta cells was assessed by EndoC-βH1 cell homogenates (C). Supplementary material 1 (PDF 55 kb)

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Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Ewa Hellström-Lindahl
    • 1
  • Angelika Danielsson
    • 2
    • 3
  • Fredrik Ponten
    • 2
  • Paul Czernichow
    • 4
  • Olle Korsgren
    • 2
  • Lars Johansson
    • 5
  • Olof Eriksson
    • 1
  1. 1.Department of Medicinal Chemistry, Preclinical PET PlatformUppsala UniversityUppsalaSweden
  2. 2.Department of Immunology, Genetics and PathologyUppsala UniversityUppsalaSweden
  3. 3.Science for Life Laboratory, Rudbeck LaboratoryUppsala UniversityUppsalaSweden
  4. 4.EndocellsParisFrance
  5. 5.Department of Radiology, Oncology and Radiation SciencesUppsala UniversityUppsalaSweden

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