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: Ryouta Kogure, Kazuya Toyama, Shuichi Hiyamuta, Itaru Kojima, Shigeki Takeda
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 416 Issue 1-2 Pg. 58-63 (Dec 09 2011) ISSN: 1090-2104 [Electronic] United States
• PMID: 22079287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• GPR119 protein, human
• Hypoglycemic Agents
• Insulin
• RNA, Small Interfering
• Receptors, G-Protein-Coupled
• Recombinant Proteins
• 5-hydroxy-6,8,11,14,17-eicosapentaenoic acid
• Eicosapentaenoic Acid
• Cyclic AMP
• Glucose

Topics

• Animals
• Cell Line, Tumor
• Cyclic AMP (metabolism)
• Diabetes Mellitus (metabolism)
• Eicosapentaenoic Acid (analogs & derivatives, chemistry, metabolism, pharmacology)
• Glucose (metabolism)
• Humans
• Hypoglycemic Agents (chemistry, metabolism, pharmacology)
• Insulin (metabolism)
• Insulin Secretion
• Mice
• RNA, Small Interfering (genetics)
• Receptors, G-Protein-Coupled (agonists, genetics, metabolism)
• Recombinant Proteins (agonists, genetics, metabolism)