Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1

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Abstract

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-1 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, MDL12330A, significantly suppressed bile acid-promoted GLP-1 secretion, suggesting that bile acids induce GLP-1 secretion via intracellular cAMP production in STC-1 cells.

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Materials and methods

Materials. Lithocholic acid and deoxycholic acid were from Nacalai Tesque. Linolenic acid, 8-bromo-cAMP, and MDL12330A were obtained from Sigma. Forskolin and Cholera toxin were purchased form Calbiochem.

Cell culture. Murine enteroendocrine cell line STC-1 [10] was maintained in Dulbecco’s modified Eagle’s medium (DMEM) containing 15% (v/v) horse serum (HS) and 5% (v/v) fetal bovine serum (FBS).

Real-time PCR analysis. Total RNA was isolated using Isogen (Nippon Gene) and subjected to polymerase

Bile acids promote GLP-1 secretion in a murine enteroendocrine cell line STC-1 through TGR5

Recently, we showed that unsaturated free fatty acid, such as linolenic acid, promoted GLP-1 secretion in murine intestinal STC-1 cells [11]. To date, however, it has not been reported that bile acids promote GLP-1 release in intestinal cultured cells. In the present study, we examined whether bile acids promote GLP-1 secretion in STC-1 cells. As shown in Fig. 1, we first confirmed that linolenic acid-induced the release of GLP-1 in STC-1 cells. Also, we found that two bile acids, lithocholic

Acknowledgments

This study was performed through Special Coordination Funds for Promoting Science and Technology from the Ministry of Education, Culture, Sports, Science and Technology, the Japanese Government. S.K. is supported by the 21st Century COE Program “Knowledge Information Infrastructure for Genome Science.”

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