کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2042202 | 1073189 | 2014 | 7 صفحه PDF | دانلود رایگان |
• Bacterial metabolite indole modulates secretion of incretin peptide GLP-1
• Indole widens the width of action potentials fired by L cells and elevates GLP-1
• Prolonged exposure to indole inhibits ATP production and thus GLP-1 secretion
SummaryIt 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.
Graphical AbstractFigure optionsDownload as PowerPoint slide
Journal: - Volume 9, Issue 4, 20 November 2014, Pages 1202–1208