TGR5 potentiates GLP-1 secretion in response to anionic exchange resins

Taoufiq Harach, Thijs W.H. Pols, Mitsunori Nomura, Adriano Maida, Mitsuhiro Watanabe, Johan Auwerx, Kristina Schoonjans

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109 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number430
JournalScientific reports
Volume2
DOIs
Publication statusPublished - 2012

ASJC Scopus subject areas

  • General

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    Harach, T., Pols, T. W. H., Nomura, M., Maida, A., Watanabe, M., Auwerx, J., & Schoonjans, K. (2012). TGR5 potentiates GLP-1 secretion in response to anionic exchange resins. Scientific reports, 2, [430]. https://doi.org/10.1038/srep00430