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Cell Rep. 2014 Nov 20;9(4):1202-8. doi: 10.1016/j.celrep.2014.10.032. Epub 2014 Nov 13.

Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells.

Author information

1
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.
2
Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
3
Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
4
Cavendish Laboratory, Department of Physics, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE, UK.
5
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.
6
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.

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.

PMID:
25456122
PMCID:
PMC4308618
DOI:
10.1016/j.celrep.2014.10.032
[Indexed for MEDLINE]
Free PMC Article

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