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 , a light-controllable GPR40 agonist based on Gw-9508. is a potent GPR40 agonist in the -configuration and can be inactivated on isomerization to with UV-A light. Irradiation with blue light reverses this effect, allowing activity to be cycled ON and OFF with a high degree of spatiotemporal precision. In dissociated primary mouse β-cells, also inactivates voltage-activated and ATP-sensitive K channels, and allows us to control glucose-stimulated Ca oscillations in whole islets with light. As such, 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.