Harach, TaoufiqPols, Thijs W. H.Nomura, MitsunoriMaida, AdrianoWatanabe, MitsuhiroAuwerx, JohanSchoonjans, Kristina2012-06-062012-06-062012-06-06201210.1038/srep00430https://infoscience.epfl.ch/handle/20.500.14299/81359WOS:000304776100001Anionic 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.Glucagon-Like Peptide-1Bile-Acid ReceptorType-2 Diabetes-MellitusProglucagon Gene-ExpressionGastrin-Releasing-PeptideEnteroendocrine Cell-LineGlycemic ControlColesevelam HclInsulin-ResistanceLdl Cholesteroltext::journal::journal article::research article