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Free fatty acid receptors and their physiological role in metabolic regulation Hirasawa A; Hara T; Ichimura A; Tsujimoto GYakugaku Zasshi 2011[]; 131 (12): 1683-9Free fatty acids (FFAs) are not only essential nutrient components, but they also function as signaling molecules in various physiological processes. In the progression of genomic analysis, many orphan G-protein coupled receptors (GPCRs) are found. Recently, GPCRs deorphanizing strategy successfully identified multiple receptors for FFAs. In these FFA receptors (FFARs), GPR40 (FFAR1) and GPR120 are activated by medium- to long- chain FFAs. GPR40 is expressed mainly in pancreatic beta-cell and mediates insulin secretion, whereas GPR120 is expressed abundantly in the intestine and regulates the secretion of cholecystokinin (CCK) and glucagons-like peptide-1 (GLP-1), it promotes insulin secretion. Due to these biological activity, GPR40 and GPR120 are potential drug target for type 2 diabetes and selective ligands have been developed. In this review, we provide recent development in the field and discuss their physiological roles and their potential as drug targets.|Animals[MESH]|Cholecystokinin/metabolism[MESH]|Diabetes Mellitus, Type 2/drug therapy/etiology[MESH]|Fatty Acids, Nonesterified/physiology[MESH]|Glucagon-Like Peptide 1/metabolism[MESH]|Humans[MESH]|Insulin Secretion[MESH]|Insulin-Secreting Cells/metabolism[MESH]|Insulin/metabolism[MESH]|Intestinal Mucosa/metabolism[MESH]|Ligands[MESH]|Mice[MESH]|Molecular Targeted Therapy[MESH]|Receptors, G-Protein-Coupled/metabolism/*physiology[MESH]|Signal Transduction[MESH]|Structure-Activity Relationship[MESH] |
