Abstract
Background: FFAR1/GPR40 is a potential target to enhance insulin secretion in type 2 diabetes, yet knowledge of the pharmacobiology of GPR40 remains incomplete. Results: GPR40 functions via both G protein-mediated and β-arrestin-mediated mechanisms; endogenous and synthetic ligands differentially engage these pathways to promote insulin secretion. Conclusion: GPR40 is subject to functionally relevant biased agonism. Significance: Biased agonism at GPR40 could be exploited for therapeutic purposes.