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Bacterial Metabolite Indole Modulates Incretin Secretion from Intestinal Enteroendocrine L Cells

2014; Cell Press; Volume: 9; Issue: 4 Linguagem: Inglês

10.1016/j.celrep.2014.10.032

2639-1856

Catalin Chimerel, Edward C. Emery, David Summers, Ulrich F. Keyser, Fiona M. Gribble, Frank Reimann,

Pancreatic function and diabetes

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 Ca2+ 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.