Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120
Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120
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DOI：
10.1038/nm1168
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发表时间：
2005-01-01
期刊：
影响因子：
82.9
通讯作者：
Tsujimoto, G
中科院分区：
文献类型：
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作者：
Hirasawa, A;Tsumaya, K;Tsujimoto, G
糖尿病是一种身体无法正常产生或使用胰岛素的疾病，是一个严重的全球健康问题(1-3)。响应食物摄入而分泌的肠道多肽，例如胰高血糖素样肽-1 (GLP-1)，是有效的肠促胰岛素激素，可增强胰腺 β 细胞葡萄糖依赖性胰岛素分泌 (4-6)。游离脂肪酸 (FFA) 提供重要的能量来源，并且在各种细胞过程中充当信号分子，包括肠道肠降血糖素肽的分泌 (7,8)。在这里，我们展示了一种在肠道中大量表达的 G 蛋白偶联受体 GPR120，其功能是作为不饱和长链 FFA 的受体。此外，我们发现 FFA 对 GPR120 的刺激可促进体外和体内 GLP-1 的分泌，并增加循环胰岛素。由于 GLP-1 是最有效的促胰岛素肠促胰岛素 (9,10)，因此我们的结果表明膳食 FFA 诱导的 GPR120 介导的 GLP-1 分泌在糖尿病的治疗中非常重要。
Diabetes, a disease in which the body does not produce or use insulin properly, is a serious global health problem(1-3). Gut polypeptides secreted in response to food intake, such as glucagon-like peptide-1 (GLP-1), are potent incretin hormones that enhance the glucose-dependent secretion of insulin from pancreatic beta cells(4-6). Free fatty acids (FFAs) provide an important energy source and also act as signaling molecules in various cellular processes, including the secretion of gut incretin peptides(7,8). Here we show that a G-protein-coupled receptor, GPR120, which is abundantly expressed in intestine, functions as a receptor for unsaturated long-chain FFAs. Furthermore, we show that the stimulation of GPR120 by FFAs promotes the secretion of GLP-1 in vitro and in vivo, and increases circulating insulin. Because GLP-1 is the most potent insulinotropic incretin(9,10), our results indicate that GPR120-mediated GLP-1 secretion induced by dietary FFAs is important in the treatment of diabetes.