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 GPR120Akira Hirasawa1, 2, 3, Keiko Tsumaya1, Takeo Awaji4, Susumu Katsuma5, Tetsuya Adachi5, Masateru Yamada1, Yukihiko Sugimoto6, Shunichi Miyazaki4
& Gozoh Tsujimoto2, 31
Department of Molecular, Cell Pharmacology, National Research Institute for Child Health and Development, 3-35-31, Taishi-do, Setagaya-ku, Tokyo 154-8567, Japan. 2
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan. 3
Shinanomachi Research Park 7S7, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. 4
Department of Physiology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. 5
Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan. 6
Department of Physiological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Correspondence should be addressed to Gozoh Tsujimoto gtsuji@pharm.kyoto-u.ac.jpDiabetes, 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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