TGR5 potentiates GLP-1 secretion in response to anionic exchange resins
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.
Keywords: Glucagon-Like Peptide-1 ; Bile-Acid Receptor ; Type-2 Diabetes-Mellitus ; Proglucagon Gene-Expression ; Gastrin-Releasing-Peptide ; Enteroendocrine Cell-Line ; Glycemic Control ; Colesevelam Hcl ; Insulin-Resistance ; Ldl Cholesterol
Record created on 2012-06-06, modified on 2016-08-09