Journal
CELL METABOLISM
Volume 25, Issue 5, Pages 1075-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2017.04.013
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Funding
- Fondation pour la Recherche Medicale
- Novo-Nordisk
- Sanofi-Aventis
- Region Midi Pyrenees
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Glucagon-like peptide-1 (GLP-1)-based therapies control glycemia in type 2 diabetic (T2D) patients. However, in some patients the treatment must be discontinued, defining a state of GLP-1 resistance. In animal models we identified a specific set of ileum bacteria impairing the GLP-1-activated gut-brain axis for the control of insulin secretion and gastric emptying. Using prediction algorithms, we identified bacterial pathways related to amino acid metabolism and transport system modules associated to GLP-1 resistance. The conventionalization of germ-free mice demonstrated their role in enteric neuron biology and the gut-brain-periphery axis. Altogether, insulin secretion and gastric emptying require functional GLP-1 receptor and neuronal nitric oxide synthase in the enteric nervous system within a eubiotic gut microbiota environment. Our data open a novel route to improve GLP-1-based therapies.
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