Optical control of GPR40 signalling in pancreatic β-cells.

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 e

SUBMITTER: Frank JA 

PROVIDER: S-EPMC5848828 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature