Figure 6. Schematic model of insulinotropic action of fasiglifam in cooperativity with endogenous FFAs in β cells FFAR1 activation by endogenous FFAs contributes to glucose-stimulated insulin secretion (GSIS) in vivo (left).

Fasiglifam treatment potentiates FFA-induced insulin secretion as an allosteric modulator, whereas FFAs also augment the activity of fasiglifam, showing reciprocal positive cooperativity (middle). Fasiglifam treatment in the absence of FFAs (nonphysiological) results in partial activation of FFAR1 and weak potentiation of GSIS (right).