Issue 11, 2017

Optical control of GPR40 signalling in pancreatic β-cells


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.

Graphical abstract: Optical control of GPR40 signalling in pancreatic β-cells

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Article information

Article type
Edge Article
02 Apr 2017
29 Aug 2017
First published
30 Aug 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 7604-7610

Optical control of GPR40 signalling in pancreatic β-cells

J. A. Frank, D. A. Yushchenko, N. H. F. Fine, M. Duca, M. Citir, J. Broichhagen, D. J. Hodson, C. Schultz and D. Trauner, Chem. Sci., 2017, 8, 7604 DOI: 10.1039/C7SC01475A

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