Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion

Fatty acids augment the glucose triggered secretion of insulin through two mechanisms: intracellular metabolism and activation of FFAR1 (GPR40), a G-protein coupled receptor. Based on studies with inhibitors of G proteins such as pertussis toxin FFAR1 is believed to signal through Gq/11. Binding of free fatty acids by FFAR1 activates the heterotrimeric Gq complex which then activates Phospholipase C, producing inositol 1,4,5-trisphosphate and eventually causing the release of intracellular calcium into the cytosol. From experiments in knockout mice it is estimated that signaling through FFAR1 is responsible for about 50% of the augmentation of insulin secretion produced by free fatty acids.

Summary from Reactome (R-HSA-434316), read 2026-09-23.