Identification of a regulatory pathway of L-phenylalanine-induced GLP-1 secretion in the enteroendocrine L cells
Identification of a regulatory pathway of L-phenylalanine-induced GLP-1 secretion in the enteroendocrine L cells
复制标题
L-苯丙氨酸诱导肠内分泌L细胞分泌GLP-1的调节途径的鉴定
DOI：
10.1016/j.bbrc.2021.12.043
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发表时间：
2022
影响因子：
3.1
通讯作者：
Tsuboi Takashi
中科院分区：
文献类型：
--
作者：
Osuga Yuri;Harada Kazuki;Tsuboi Takashi
胰高血糖素样肽-1（GLP-1）是肠促胰岛素激素之一，由肠内分泌L细胞感受胰高血糖素、氨基酸和脂肪酸而分泌。一些氨基酸已显示可促进GLP-1从小肠肠内分泌L细胞分泌。然而，L-苯丙氨酸（GLP-1分泌的有效触发剂）导致肠内分泌L细胞分泌GLP-1的分子机制尚未阐明。在这项研究中，我们使用活细胞成像来阐明L-苯丙氨酸激活肠内分泌L细胞的途径。结果表明，L-苯丙氨酸可被Gq偶联受体GPR 142感受，引起细胞内Ca ~（2+）浓度升高。此外，L-苯丙氨酸通过Na+依赖性氨基酸转运蛋白直接进入细胞，引起膜去极化并增强GLP-1分泌。总之，肠内分泌L细胞可能通过检测管腔中的L-苯丙氨酸并通过GPR 142和Na+依赖性氨基酸转运蛋白分泌GLP-1来调节体内血糖水平。
Glucagon like peptide-1 (GLP-1) is one of incretin hormone and is secreted when enteroendocrine L cells sense saccharides, amino acids, and fatty acids. Some amino acids have been shown to promote GLP-1 secretion from small intestinal enteroendocrine L cells. However, the molecular mechanisms that L-phenylalanine, a potent trigger of GLP-1 secretion, causes GLP-1 secretion from enteroendocrine L cells has not been elucidated. In this study, we used live-cell imaging to clarify the pathway by which L-phenylalanine activates enteroendocrine L cells. The results showed that L-phenylalanine was sensed by Gq-coupled receptor GPR142 and caused an increase in intracellular Ca2+concentration. In addition, L-phenylalanine was taken up directly into the cell via Na+-dependent amino acid transporter, causing membrane depolarization and enhancing GLP-1 secretion. In summary, enteroendocrine L cells may regulate blood glucose levels in the body by detecting L-phenylalanine in the lumen and secreting GLP-1 via GPR142 and Na+-dependent amino acid transporters.