5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion
5-Hydroxy-eicosapentaenoic acid is an endogenous GPR119 agonist and enhances glucose-dependent insulin secretion
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DOI：
10.1016/j.bbrc.2011.10.141
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发表时间：
2011-12-09
影响因子：
3.1
通讯作者：
Takeda, Shigeki
中科院分区：
文献类型：
--
作者：
Kogure, Ryouta;Toyama, Kazuya;Takeda, Shigeki
GPR119是表达于胰岛β细胞和肠道内分泌细胞的G蛋白偶联受体之一。因为GPR119的激动剂刺激依赖葡萄糖的胰岛素分泌。GPR119激动剂有望促进抗糖尿病效果和控制血糖稳态。在这里，我们报道了一种omega-3不饱和脂肪酸代谢产物，5-羟基二十碳五烯酸(5-HEPE)，是一种有效的GPR119激动剂，并促进葡萄糖依赖的胰岛素分泌。5-HEPE可促进小鼠胰岛素瘤细胞和人肠腺癌细胞内cAMP的积聚。这些效应被GPR119特异的siRNA钝化。重组GPR119对5-HEPE和正品激动剂也有反应。之前的几份报告表明了omega-3不饱和脂肪酸的有益生物效应，流行病学研究表明，这些脂肪酸对糖尿病具有保护作用。然而，omega-3不饱和脂肪酸及其代谢物的分子药理和受体鉴定尚未得到很好的研究。希望我们的发现将鼓励对omega-3脂肪酸和糖尿病之间的分子关系进行新的研究。(C)2011 Elsevier Inc.保留所有权利。
GPR119 is one of the G-protein-coupled receptors expressed in pancreatic beta-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. (C) 2011 Elsevier Inc. All rights reserved.