Figure 4

TGR5 signaling is induced by colon content of mice treated with AERs.

(a) GLP-1 release from explants of different intestinal segments of TGR5^+/+ mice. Duodenum (duo). (b) GLP-1 release from colon explants of TGR5^+/+ and TGR5^−/− mice (n = 6 per group) in response to 1 hour treatment with 30 µM INT-777 or 15 µM LCA/DCA. Mice were fed a high fat diet for 10 weeks prior to the collection of explants. (c) GLP-1 secretion from colon explants of TGR5^+/+ and TGR5^−/− mice fed a high fat diet for 2 weeks and subsequently treated with Colestilan for two additional weeks (n = 6 per group). (d) Luciferase activity in CHO cells transiently transfected with TGR5 expression vector and a cAMP response element (CRE)-driven luciferase reporter vector. Cells were treated with DMSO vehicle (white bars), 10 µM litocholic acid (LCA; black bars), colon content collected from untreated wildtype mice (light gray bars), or colon content collected from Colestilan-treated wildtype mice (dark gray bars; n = 5 per group). The mice cohorts used for the collection of colon content were fed a high fat diet for 10 weeks prior treatment with Colestilan for 2 weeks. (e) GLP-1 release from colon explants of TGR5^+/+ and TGR5^−/− mice (n = 6 per group) in response to 1 hour exposure of colon content derived from untreated wildtype mice (light gray bars), or colon content collected from Colestilan-treated wildtype mice (n = 5 per group). Data represent mean ± SE. *Statistically significant, p<0.05; **: p<0.01.