Role for TGR5 in mediating anti-diabetic actions of resin drugs.
© 2012 A.D.A.M.
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, the group of Prof. Kristina Schoonjans(Laboratory of Integrative Systems Physiology) 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. They identified the colon as a major source of GLP-1 secretion after resin treatment. Furthermore, they 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.