title: [Free fatty acid receptors and their physiological role in metabolic regulation].
abstract: Free 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 β-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.
authors: Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan. akira_h@pharm.kyoto-u.ac.jp
authors: Akira
authors: A
authors: Hirasawa
authors: Takafumi
authors: T
authors: Hara
authors: Atsuhiko
authors: A
authors: Ichimura
authors: Gozoh
authors: G
authors: Tsujimoto
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000209:etiology; D005230:Fatty Acids, Nonesterified / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D008024:Ligands; D051379:Mice; D058990:Molecular Targeted Therapy; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: C473034:FFAR1 protein, human; C519853:FFAR4 protein, human; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1; D002766:Cholecystokinin