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

Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM, Reimann F - Cell Rep (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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Effect of Indole on KCl Stimulated GLP-1 Secretion(A) Cumulative GLP-1 secretion from GLUTag cells stimulated with 30 mM KCl, measured at different time points. Cells were incubated with and without 1 mM indole, and secretion was normalized to the 60 min, 30 mM KCl time point (average value 232 pg/ml) from the same experiment. Each data point was calculated by averaging over six independent measurements.(B) Calculated rates of GLP-1 secretion over the time periods indicated, calculated from the measurements obtained in (A).Data represent the mean ± SEM. **p < 0.01, ***p < 0.001 by Student’s t test.
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Figure 4: Effect of Indole on KCl Stimulated GLP-1 Secretion(A) Cumulative GLP-1 secretion from GLUTag cells stimulated with 30 mM KCl, measured at different time points. Cells were incubated with and without 1 mM indole, and secretion was normalized to the 60 min, 30 mM KCl time point (average value 232 pg/ml) from the same experiment. Each data point was calculated by averaging over six independent measurements.(B) Calculated rates of GLP-1 secretion over the time periods indicated, calculated from the measurements obtained in (A).Data represent the mean ± SEM. **p < 0.01, ***p < 0.001 by Student’s t test.

Mentions: We showed previously that GLP-1 secretion by GLUTag cells is strongly stimulated by increasing the extracellular K+ concentration, which results in membrane depolarization and voltagegated Ca2+ entry (Friedlander et al., 2011; Reimann et al., 2005). At the same time this is an ATP-demanding process, as energy is required to sustain the high rate of GLP-1 release. When GLUTag cells were incubated in the presence of 30 mM KCl, GLP-1 secretion increased 13-fold compared with that measured from cells in 4.5 mM KCl, as measured by cumulative secretion over 60 min. As evident from Figure 4, 1 mM indole did not affect cumulative GLP-1 secretion within the first 5 min of exposure to KCl, but reduced cumulative release after 15 min by 25% and after 60 min by ~70%. When these data were represented as the rates of secretion during different time intervals, it was evident that indole did not affect the GLP-1 secretory rate during the first 5 min of exposure to 30 mM KCl, but drastically reduced secretion in the 5–15 min interval and beyond.


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

Chimerel C, Emery E, Summers DK, Keyser U, Gribble FM, Reimann F - Cell Rep (2014)

Effect of Indole on KCl Stimulated GLP-1 Secretion(A) Cumulative GLP-1 secretion from GLUTag cells stimulated with 30 mM KCl, measured at different time points. Cells were incubated with and without 1 mM indole, and secretion was normalized to the 60 min, 30 mM KCl time point (average value 232 pg/ml) from the same experiment. Each data point was calculated by averaging over six independent measurements.(B) Calculated rates of GLP-1 secretion over the time periods indicated, calculated from the measurements obtained in (A).Data represent the mean ± SEM. **p < 0.01, ***p < 0.001 by Student’s t test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4308618&req=5

Figure 4: Effect of Indole on KCl Stimulated GLP-1 Secretion(A) Cumulative GLP-1 secretion from GLUTag cells stimulated with 30 mM KCl, measured at different time points. Cells were incubated with and without 1 mM indole, and secretion was normalized to the 60 min, 30 mM KCl time point (average value 232 pg/ml) from the same experiment. Each data point was calculated by averaging over six independent measurements.(B) Calculated rates of GLP-1 secretion over the time periods indicated, calculated from the measurements obtained in (A).Data represent the mean ± SEM. **p < 0.01, ***p < 0.001 by Student’s t test.
Mentions: We showed previously that GLP-1 secretion by GLUTag cells is strongly stimulated by increasing the extracellular K+ concentration, which results in membrane depolarization and voltagegated Ca2+ entry (Friedlander et al., 2011; Reimann et al., 2005). At the same time this is an ATP-demanding process, as energy is required to sustain the high rate of GLP-1 release. When GLUTag cells were incubated in the presence of 30 mM KCl, GLP-1 secretion increased 13-fold compared with that measured from cells in 4.5 mM KCl, as measured by cumulative secretion over 60 min. As evident from Figure 4, 1 mM indole did not affect cumulative GLP-1 secretion within the first 5 min of exposure to KCl, but reduced cumulative release after 15 min by 25% and after 60 min by ~70%. When these data were represented as the rates of secretion during different time intervals, it was evident that indole did not affect the GLP-1 secretory rate during the first 5 min of exposure to 30 mM KCl, but drastically reduced secretion in the 5–15 min interval and beyond.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

Show MeSH
Related in: MedlinePlus