SFEBES2021 Oral Communications Metabolism, Obesity and Diabetes (6 abstracts)
Microbial tryptophan metabolites modulate L-cell induced GLP-1 secretion to improve glucose homeostasis
Phyllis Phuah 1 , Sijing Cheng 1 , Mariana Norton 1 , Anna Roberts 1 , Emile Otsubo 1 , Fiona Gribble 2 , Frank Reimann 2 , Aylin Hanyaloglu 1 , Bryn Owen 1 & Kevin Murphy 1
1Imperial College London, London, United Kingdom; 2University of Cambridge, Cambridge, United Kingdom
Growing evidence implicates gut microbiota-derived metabolites in metabolic homeostasis. Gut microbial dysbiosis occurs in obesity, while high-fibre and high-protein diets, which improve glucose tolerance and induce weight loss, are associated with the generation of microbial metabolites. Understanding how the gut responds to microbial metabolites may identify mechanisms that induce satiety and improve glucoregulation, revealing novel therapeutic targets. Indole is generated following bacterial catabolism of the essential amino acid L-tryptophan, and can act as an agonist of the aryl hydrocarbon receptor. Indole has been reported to modulate glucagon-like peptide 1 (GLP-1) secretion in vitro, while recent epidemiological studies found that indole metabolites are inversely associated with type 2 diabetes incidence. We investigated the effect of indole on food intake, glucose tolerance and gut hormone secretion in mice. Acute oral but not intraperitoneal administration of indole significantly improved glucose tolerance in vivo, but orally administered indole had no effect on food intake in mice. In accord with this improvement in glucose tolerance, indole stimulated the secretion of GLP-1 from STC-1 cells and primary murine colonic crypts in vitro, an effect that did not appear to involve the aryl hydrocarbon receptor, but was attenuated by Transient Receptor Potential A1 ion channel inhibition. Additionally, using murine intestinal organoids which express a fluorescent calcium reporter in enteroendocrine L-cells, we found that indole dose dependently increased calcium mobilization in L-cells. Single bolus oral supplementation of indole also caused an improvement in glucose tolerance which lasted for several days. In line with this, increased expression of Gcg, which codes for GLP-1, was detected in the ileum of indole-treated mice. Further work is needed to elucidate how indole metabolites acutely and sub-chronically modulate the enteroendocrine system to determine whether this pathway is conserved in humans, and whether it can be exploited therapeutically.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more