Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1.
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.
Katsuma
Susumu
S
Bioinformatics Center, Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
Hirasawa
Akira
A
Tsujimoto
Gozoh
G
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019858:Enteroendocrine Cells / Q000166:cytology*; D005822:Genetic Vectors; D005934:Glucagon / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1; D007097:Imines / Q000494:pharmacology; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D012313:RNA / Q000737:chemistry; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D014162:Transfection; D017962:alpha-Linolenic Acid / Q000737:chemistry
D000067956:Adenylyl Cyclase Inhibitors; D001647:Bile Acids and Salts; C473772:GPBAR1 protein, human; D007097:Imines; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017962:alpha-Linolenic Acid; D012313:RNA; C014925:RMI 12330A; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000242:Cyclic AMP