title: 5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion.
abstract: GPR119 is one of the G-protein-coupled receptors expressed in pancreatic β-cells and intestinal endocrine cells. Since agonists to GPR119 stimulate glucose-dependent insulin secretion, GPR119 agonists are anticipated to promote anti-diabetic effects and control of glucose homeostasis. Here, we reported that an omega-3 unsaturated fatty acid metabolite, 5-hydroxy-eicosapentaenoic acid (5-HEPE), was a potent agonist for GPR119 and enhanced glucose-dependent insulin secretion. 5-HEPE stimulated cAMP accumulation in mouse MIN6 insulinoma cells and human HuTu80 intestinal adenocarcinoma cells. These effects were blunted by GPR119-specific siRNA. Recombinant GPR119 also responded to 5-HEPE as well as authentic agonists. Several previous reports have indicated the beneficial biological effects of omega-3 unsaturated fatty acids, and epidemiological studies have suggested that these fatty acids plays a protective role against diabetes. However, the molecular pharmacology and receptor identifications of omega-3 unsaturated fatty acids and their metabolites have not yet been well investigated. It is hoped that our findings will encourage novel investigations into the molecular relationships between omega-3 fatty acids and diabetes.
authors.affiliation: Department of Chemical Biology, Graduate School of Engineering, Gunma University, Kiryu, Gunma 376-8515, Japan.
authors.forename: Ryouta
authors.initials: R
authors.lastname: Kogure
authors.forename: Kazuya
authors.initials: K
authors.lastname: Toyama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hiyamuta
authors.forename: Itaru
authors.initials: I
authors.lastname: Kojima
authors.forename: Shigeki
authors.initials: S
authors.lastname: Takeda
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D000242:Cyclic AMP / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: C519854:GPR119 protein, human; D007004:Hypoglycemic Agents; D007328:Insulin; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; C058722:5-hydroxy-6,8,11,14,17-eicosapentaenoic acid; D015118:Eicosapentaenoic Acid; D000242:Cyclic AMP; D005947:Glucose