Figure 1.

Regulation of insulin secretion by short-chain fatty acids (SCFAs) through receptors FFA2 and FFA3. SCFAs can bind to both receptors either amplifying (in blue) or diminishing (in golden) glucose-stimulated insulin secretion (GSIS). Upon ligand activation of FFA2, Gαq/11 subunits activate PLC, which hydrolyzes PIP₂ to DAG and IP₃. In turn, DAG activates protein kinase C (PKC) and IP₃ releases Ca²⁺ from ER stores, both amplifying the insulin release. FFA2, like FFA3, can also couple with Gαi/o subunits and inhibit AC, which decreases cAMP level, inhibiting PKA and EPAC-mediated insulin release [18,37]. Adopted with permission from Trends Endocrinol Metab (License No. 4724910996230).