Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1
Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1
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DOI：
10.1016/j.bbrc.2005.01.139
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发表时间：
2005-04-01
影响因子：
3.1
通讯作者：
Tsujimoto, G
中科院分区：
文献类型：
--
作者：
Katsuma, S;Hirasawa, A;Tsujimoto, G
胆汁酸在膳食脂质的吸收和胆汁酸生物合成的调节中起重要作用。最近，G蛋白偶联受体TGR 5被鉴定为细胞表面胆汁酸受体。在这项研究中，我们表明，胆汁酸促进胰高血糖素样肽-1（GLP-1）分泌通过TGR 5在小鼠肠内分泌细胞系STC-1。在STC-1细胞中，胆汁酸以剂量依赖性方式促进GLP-1分泌。由于STC-1细胞表达TGR 5 mRNA，我们研究了胆汁酸是否通过TGR 5诱导GLP-1分泌。RNA干扰实验表明，TGR 5表达减少导致GLP-1分泌减少。此外，用含有TGR 5的表达质粒瞬时转染STC-1细胞显著增强GLP-1分泌，表明胆汁酸通过STC-1细胞中的TGR 5促进GLP-1分泌。胆汁酸诱导STC-1细胞内cAMP水平的快速和剂量依赖性升高。腺苷酸环化酶抑制剂MDLI 2330 A显著抑制胆汁酸促进的GLP-1分泌，表明胆汁酸通过STC-1细胞内cAMP的产生诱导GLP-1分泌。(C)2005年爱思唯尔公司All rights reserved.
Bile acids play essential roles in the absorption of dietary lipids and in the regulation of bile acid biosynthesis. Recently, a G protein-coupled receptor, TGR5, was identified as a cell-surface bile acid receptor. In this study, we show that bile acids promote glucagon-like peptide-1 (GLP-1) secretion through TGR5 in a murine enteroendocrine cell line STC-1. In STC-1 cells, bile acids promoted GLP-I secretion in a dose-dependent manner. As STC-1 cells express TGR5 mRNA, we examined whether bile acids induce GLP-1 secretion through TGR5. RNA interference experiments showed that reduced expression of TGR5 resulted in reduced secretion of GLP-1. Furthermore, transient transfection of STC-1 cells with an expression plasmid containing TGR5 significantly enhanced GLP-1 secretion, indicating that bile acids promote GLP-1 secretion through TGR5 in STC-1 cells. Bile acids induced rapid and dose-dependent elevation of intracellular cAMP levels in STC-1 cells. An adenylate cyclase inhibitor, MDLI2330A, significantly suppressed bile acid-promoted GLP-I secretion, suggesting that bile acids induce GLP-1 secretion via intracellular cAMP production in STC-1 cells. (C) 2005 Elsevier Inc. All rights reserved.