TABLE 7

Differential modulation of agonist binding at the human GLP-1R Met149 receptor variant by compound 2

Data were analyzed using a three-parameter logistic equation as defined in eq. 1. pIC50 values represent the negative logarithm of the concentration of agonist that inhibits binding of half the total concentration of radiolabeled antagonist, 125I-exendin(9–39). All data are normalized to the maximum 125I-exendin(9–39) binding in each individual data set, with non-specific binding measured in the presence of 1 μM exendin(9–39). All values are mean ± S.E.M. of three to four independent experiments, conducted in duplicate.

pIC50
Wild TypeMet149
Peptide+ 3 μM Compound 2Peptide+ 3 μM Compound 2
GLP-1(7–36)NH28.4 ± 0.18.9 ± 0.1*6.4 ± 0.28.4 ± 0.2*
Exendin-48.9 ± 0.19.4 ± 0.17.6 ± 0.19.0 ± 0.2*
Oxyntomodulin7.4 ± 0.18.5 ± 0.2*6.0 ± 1.07.2 ± 0.3
  • * Statistically significant, P < 0.05 compared with peptide control, paired t test.