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.
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We thank S. Mine, T. Tanaka, Y. Kitagawa and S. Suzuki for their technical assistance. This study was performed through Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government (G.T.). S.K. and T.A. are supported by the 21st Century Center of Excellence Program “Knowledge Information Infrastructure for Genome Science.”
The authors declare no competing financial interests.
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Hirasawa, A., Tsumaya, K., Awaji, T. et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 11, 90–94 (2005). https://doi.org/10.1038/nm1168
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