Access

Letter

Nature Medicine 11, 90 - 94 (2004)
Published online: 26 December 2004 | doi:10.1038/nm1168

Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120

Akira Hirasawa1,2,3, Keiko Tsumaya1, Takeo Awaji4, Susumu Katsuma5, Tetsuya Adachi5, Masateru Yamada1, Yukihiko Sugimoto6, Shunichi Miyazaki4 & Gozoh Tsujimoto2,3

Diabetes, a disease in which the body does not produce or use insulin properly, is a serious global health problem1, 2, 3. Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta cells4, 5, 6. Free fatty acids (FFAs) provide an important energy source and also act as signaling molecules in various cellular processes, including the secretion of gut incretin peptides7, 8. Here we show that a G-protein-coupled receptor, GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain FFAs. Furthermore, we show that the stimulation of GPR120 by FFAs promotes the secretion of GLP-1 in vitro and in vivo, and increases circulating insulin. Because GLP-1 is the most potent insulinotropic incretin9, 10, our results indicate that GPR120-mediated GLP-1 secretion induced by dietary FFAs is important in the treatment of diabetes.