TABLE 2.
Effects of naturally occurring human GLP-1R polymorphisms on agonist binding
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). Data are normalized to maximum 125I-exendin(9–39) binding of each individual data set, with nonspecific 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. Data were analyzed with one-way analysis of variance and Dunnett's post test.
| pIC50 |
|||
|---|---|---|---|
| GLP-1(7–36)NH2 | Exendin-4 | Oxyntomodulin | |
| Wild type | 8.9 ± 0.1 | 9.4 ± 0.1 | 7.9 ± 0.1 |
| Leu7 | 8.9 ± 0.2 | 9.5 ± 0.1 | 8.2 ± 0.1 |
| Lys20 | 8.8 ± 0.1 | 9.6 ± 0.1 | 7.9 ± 0.2 |
| His44 | 8.9 ± 0.1 | 9.5 ± 0.1 | 7.9 ± 0.1 |
| Gln131 | 8.8 ± 0.1 | 9.3 ± 0.1 | 7.9 ± 0.1 |
| Met149 | 6.5 ± 0.2* | 7.9 ± 0.2* | 5.5 ± 0.2* |
| Ser168 | 9.3 ± 0.1 | 9.5 ± 0.1 | 8.2 ± 0.1 |
| Leu260 | 9.2 ± 0.2 | 9.4 ± 0.2 | 7.9 ± 0.1 |
| Thr316 | 9.5 ± 0.2 | 9.7 ± 0.2 | 8.4 ± 0.2 |
| Cys333 | 9.0 ± 0.1 | 9.6 ± 0.1 | 8.0 ± 0.1 |
| Gln421 | 9.1 ± 0.2 | 9.6 ± 0.2 | 8.1 ± 0.2 |
*
Statistically significant at p < 0.05.