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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.

SUBMITTER: Chimerel C 

PROVIDER: S-EPMC4308618 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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

Chimerel Catalin C   Emery Edward E   Summers David K DK   Keyser Ulrich U   Gribble Fiona M FM   Reimann Frank F  

Cell reports 20141113 4


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  ...[more]

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