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

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.This is the final version. It was first published by Elsevier at http://www.cell.com/cell-reports/abstract/S2211-1247%2814%2900901-2

Passive transport through biological membranes

This thesis is not available on this repository until the author agrees to make it public. If you are the author of this thesis and would like to make your work openly available, please contact us: [email protected] Library can supply a digital copy for private research purposes; interested parties should submit the request form here: http://www.lib.cam.ac.uk/collections/departments/digital-content-unit/ordering-imagesPlease note that print copies of theses may be available for consultation in the Cambridge University Library's Manuscript reading room. Admission details are at http://www.lib.cam.ac.uk/collections/departments/manuscripts-university-archivesThe living organisms are varied when viewed from a macroscopic perspective, but on the molecular level they function based on the same fundamental principles. All living organisms are compartmented into cells via cellular walls made of lipid membranes. Through the wall the cell needs to transport nutrients, waste, genetic information and signaling molecules. The cell achieves this task via passive and active transport. In this thesis we focus on passive transport processes. In Chapter 1 of this thesis I introduce the topic of passive transport and its importance for biological systems. In Chapter 2 I use fluorescence methods to determine the passive transport of molecules with self intrinsic fluorescence through lipid membranes. We have built a unique fluorescence microscope which is capable of visualizing the fluorescence of molecules excited with deep UV light. With this new tool we monitored passive transport through the lipid membrane for several biologically significant molecules like for example the bacterial signal indole. Indole is an organic compound linked to important cellular processes like bacterial growth rates and cellular morphology. It is believed that indole is actively transported through the membrane of Escherichia coli via influx and efflux pumps. Here we give an unambiguous proof that indole can freely diffuse through intact bacterial lipid membranes. We extend this study to other molecules with self intrinsic fluorescence , like for example the antibiotic norfloxacin and the fluorescent dye fluorescein. We show that both these molecules can undergo passive transport through the lipid membrane

CCDC 1540884: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures