Gut Microbiota: FFAR Reaching Effects on Islets

The G protein-coupled receptors, free fatty acid (FFA) receptors 2 and 3 (FFA2 and FFA3), belonging to the free fatty acid receptor (FFAR) class, sense a distinct class of nutrients, short chain fatty acids (SCFAs). These receptors participate in both immune and metabolic regulation. The latter includes a role in regulating secretion of metabolic hormones. It was only recently that their role in pancreatic beta cells was recognized; these receptors are known now to affect not only insulin secretion but also beta-cell survival and proliferation. These observations make them excellent potential therapeutic targets in type 2 diabetes. Moreover, expression on both immune and beta cells makes these receptors possible targets in type 1 diabetes. Furthermore, SCFAs are generated by gut microbial fermentative activity; therefore, signaling by FFA2 and FFA3 represents an exciting novel link between the gut microbiota and the beta cells. This review enumerates the role of these receptors in beta cells revealed so far and discusses possible roles in clinical translation.