Fig. 2.
The effects of the substituted cyclobutanes are mediated through GLP-1R. (a) cAMP response element-driven luciferase activities were induced by different concentrations of GLP-1, S4P, and Boc5 in the HEK293-rGLP-1R cells. Estimated EC50 values were 68 pM, 1.08 μM, and 2.73 μM, respectively. (b) GLP-1R-mediated luciferase responses to Boc5 (10 μM), S4P (10 μM), and GLP-1 (0.05 nM) were each dose-dependently blocked by exendin(9–39). (c) Competitive inhibition of [125I]GLP-1(7–36) amide binding to GLP-1R by GLP-1, S4P, or Boc5. Estimated Ki values were 0.66 nM, 287 nM, and 1.47 μM, respectively. (d) The effect of Boc5 on the glucose-stimulated insulin secretion in rat isolated pancreatic islets. Symbols are means ± SEM in all panels. n = 4 measurements per symbol in a and d; n = 3 measurements per symbol in b and c.