Optical control of GPR40 signalling in pancreatic β-cells

James Allen Frank, Dmytro A. Yushchenko, Nicholas H.F. Fine, Margherita Duca, Mevlut Citir, Johannes Broichhagen, David J. Hodson, Carsten Schultz, Dirk Trauner

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Fatty acids activate GPR40 and K+ channels to modulate β-cell function. Herein, we describe the design and synthesis of FAAzo-10, a light-controllable GPR40 agonist based on Gw-9508. FAAzo-10 is a potent GPR40 agonist in the trans-configuration and can be inactivated on isomerization to cis with UV-A light. Irradiation with blue light reverses this effect, allowing FAAzo-10 activity to be cycled ON and OFF with a high degree of spatiotemporal precision. In dissociated primary mouse β-cells, FAAzo-10 also inactivates voltage-activated and ATP-sensitive K+ channels, and allows us to control glucose-stimulated Ca2+ oscillations in whole islets with light. As such, FAAzo-10 is a useful tool to study the complex effects, with high specificity, which FA-derivatives such as Gw-9508 exert at multiple targets in mouse β-cells.

Original languageEnglish (US)
Pages (from-to)7604-7610
Number of pages7
JournalChemical Science
Volume8
Issue number11
DOIs
StatePublished - Jan 1 2017

ASJC Scopus subject areas

  • Chemistry(all)

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    Frank, J. A., Yushchenko, D. A., Fine, N. H. F., Duca, M., Citir, M., Broichhagen, J., Hodson, D. J., Schultz, C., & Trauner, D. (2017). Optical control of GPR40 signalling in pancreatic β-cells. Chemical Science, 8(11), 7604-7610. https://doi.org/10.1039/c7sc01475a