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

authored by

Romain Bertrand, Andrea Wolf, Yuri Ivashchenko, Matthias Löhn, Matthias Schäfer, Mark Brönstrup, Martin Gotthardt, Volker Derdau, Oliver Plettenburg

Abstract

Diabetes affects an increasing number of patients worldwide and is responsible for a significant rise in healthcare expenses. Imaging of β-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 β-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 β-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 β-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.

Organisation(s)

Institute of Organic Chemistry

External Organisation(s)

Sanofi-Aventis Deutschland GmbH
Radboud University Nijmegen (RU)
Boehringer Ingelheim
Helmholtz Centre for Infection Research (HZI)
Helmholtz Zentrum München - German Research Center for Environmental Health

Type

Article

Journal

ACS chemical biology

Volume

11

Pages

1745-1754

No. of pages

10

ISSN

1554-8929

Publication date

17.06.2016

Publication status

Published

Peer reviewed

Yes

ASJC Scopus subject areas

Biochemistry, Molecular Medicine

Sustainable Development Goals

SDG 3 - Good Health and Well-being

Electronic version(s)

https://doi.org/10.1021/acschembio.5b00791 (Access: Closed)