Synthesis and Characterization of a Promising Novel FFAR1/GPR40 Targeting Fluorescent Probe for beta-Cell Imaging

Diabetes affects an increasing number of patients worldwide and is responsible for a significant rise in healthcare expenses. Imaging of beta-cells bears the potential to contribute to an improved understanding, diagnosis, and development of new treatment options for diabetes. Here, we describe the first small molecule fluorescent probe targeting the free fatty acid receptor 1 (FFAR1/GPR40). This receptor is highly expressed on beta-cells, and was up to now unexplored for imaging purposes. We designed a novel probe by facile modification of the selective and potent FFAR1 agonist TAK-875. Effective and specific binding of the probe was demonstrated using FFAR1 overexpressing cells. We also successfully labeled FFAR1 on MIN6 and INS1E cells, two widely used beta-cell models, by applying an effective amplification protocol. Finally, we showed that the probe is capable of inducing insulin secretion in a glucose-dependent manner, thus demonstrating that functional activity of the probe was maintained. These results suggest that our probe represents a first important step to successful beta-cell imaging by targeting FFAR1. The developed probe may prove to be particularly useful for in vitro and ex vivo studies of diabetic cellular and animal models to gain new insights into disease pathogenesis.

  • Bertrand, R.
  • Wolf, A.
  • Ivashchenko, Y.
  • Lohn, M.
  • Schafer, M.
  • Bronstrup, M.
  • Gotthardt, M.
  • Derdau, V.
  • Plettenburg, O.


  • Animals
  • Benzofurans/chemistry/pharmacology
  • Diabetes Mellitus/diagnostic imaging
  • Fluorescent Dyes/chemical synthesis/*chemistry/pharmacology
  • HEK293 Cells
  • Humans
  • Insulin/metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells/metabolism
  • Mice
  • Molecular Imaging
  • Rats
  • Receptors, G-Protein-Coupled/agonists/chemistry/*metabolism
  • Structure-Activity Relationship
  • Sulfones/chemistry/pharmacology
Publication details
DOI: 10.1021/acschembio.5b00791
Journal: ACS Chem Biol
Pages: 1745-54
Number: 6
Work Type: Original
Access number: 27115176
See publication on PubMed