title: Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells.
abstract: It has long been speculated that metabolites, produced by gut microbiota, influence host metabolism in health and diseases. Here, we reveal that indole, a metabolite produced from the dissimilation of tryptophan, is able to modulate the secretion of glucagon-like peptide-1 (GLP-1) from immortalized and primary mouse colonic L cells. Indole increased GLP-1 release during short exposures, but it reduced secretion over longer periods. These effects were attributed to the ability of indole to affect two key molecular mechanisms in L cells. On the one hand, indole inhibited voltage-gated K(+) channels, increased the temporal width of action potentials fired by L cells, and led to enhanced Ca(2+) entry, thereby acutely stimulating GLP-1 secretion. On the other hand, indole slowed ATP production by blocking NADH dehydrogenase, thus leading to a prolonged reduction of GLP-1 secretion. Our results identify indole as a signaling molecule by which gut microbiota communicate with L cells and influence host metabolism.
authors.affiliation: Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK; Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK. Electronic address: cc539@cam.ac.uk.
authors.forename: Catalin
authors.initials: C
authors.lastname: Chimerel
authors.affiliation: Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Emery
authors.affiliation: Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
authors.forename: David K
authors.initials: DK
authors.lastname: Summers
authors.affiliation: Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keyser
authors.affiliation: Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. Electronic address: fmg23@cam.ac.uk.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Gribble
authors.affiliation: Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK. Electronic address: fr222@cam.ac.uk.
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003106:Colon / Q000166:cytology; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D054795:Incretins / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology*; D007477:Ions; D051379:Mice; D009249:NADP / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology
chemical_list: D054795:Incretins; D007211:Indoles; D007477:Ions; D024642:Potassium Channels, Voltage-Gated; D009249:NADP; D000244:Adenosine Diphosphate; D011189:Potassium Chloride; C030374:indole; D052216:Glucagon-Like Peptide 1; D000255:Adenosine Triphosphate; D002118:Calcium