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TGR5 potentiates GLP-1 secretion in response to anionic exchange resins
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TGR5 potentiates GLP-1 secretion in response to anionic exchange resins
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Journal Article
TGR5 potentiates GLP-1 secretion in response to anionic exchange resins
2012
Overview
Anionic exchange resins are
bona fide
cholesterol-lowering agents with glycemia lowering actions in diabetic patients. Potentiation of intestinal GLP-1 secretion has been proposed to contribute to the glycemia lowering effect of these non-systemic drugs. Here, we show that resin exposure enhances GLP-1 secretion and improves glycemic control in diet-induced animal models of “diabesity”, effects which are critically dependent on TGR5, a G protein-coupled receptor that is activated by bile acids. We identified the colon as a major source of GLP-1 secretion after resin treatment. Furthermore, we demonstrate that the boost in GLP-1 release by resins is due to both enhanced TGR5-dependent production of the precursor transcript of GLP-1 as well as to the local enrichment of TGR5 agonists in the colon. Thus, TGR5 represents an essential component in the pathway mediating the enhanced GLP-1 release in response to anionic exchange resins.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 631/443
/ Animals
/ Anion Exchange Resins - pharmacology
/ Bile Acids and Salts - pharmacology
/ Colon
/ Diet, High-Fat - adverse effects
/ Enteroendocrine Cells - drug effects
/ Enteroendocrine Cells - metabolism
/ Glucagon-Like Peptide 1 - blood
/ Glucagon-Like Peptide 1 - genetics
/ Glucagon-Like Peptide 1 - metabolism
/ Humanities and Social Sciences
/ Insulin Resistance - genetics
/ Male
/ Mice
/ Receptors, G-Protein-Coupled - genetics
/ Receptors, G-Protein-Coupled - metabolism
/ Resins
/ Reverse Transcriptase Polymerase Chain Reaction
/ Science
