期刊
SCIENTIFIC REPORTS
卷 2, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep00430
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资金
- Ecole Polytechnique Federale de Lausanne
- Swiss National Science Foundation [31003A_125487]
- Nestle
- FEBS
- AXA
- Canadian Institutes of Health Research
- Swiss National Science Foundation (SNF) [31003A_125487] Funding Source: Swiss National Science Foundation (SNF)
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.
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