TABLE 4.
Effects of naturally occurring human GLP-1R polymorphisms on agonist signaling via intracellular Ca2+ mobilization
Data were analyzed using a three-parameter logistic equation as defined in eq. 1. pEC50 values represent the negative logarithm of the concentration of agonist that produces half the maximal response. Emax represents the maximal response normalized to the response elicited by that of 10−4 M ATP. All values are mean ± S.E.M. of 5 to 10 independent experiments, conducted in duplicate. Data were analyzed with one-way analysis of variance and Dunnett's post test.
| Intracellular Ca2+ Mobilization |
||||||
|---|---|---|---|---|---|---|
| pEC50 |
Emax |
|||||
| GLP-1(7–36)NH2 | Exendin-4 | Oxyntomodulin | GLP-1(7–36)NH2 | Exendin-4 | Oxyntomodulina | |
| Wild type | 7.8 ± 0.2 | 8.0 ± 0.3 | N.D. | 25.8 ± 1.5 | 23.1 ± 2.5 | 25.9 ± 5.5 |
| Leu7 | 8.0 ± 0.2 | 7.9 ± 0.2 | N.D. | 25.2 ± 1.4 | 20.4 ± 1.4 | 21.0 ± 2.5 |
| Lys20 | 7.9 ± 0.2 | 8.1 ± 0.1 | N.D. | 21.3 ± 1.4 | 15.0 ± 0.7* | 15.7 ± 1.6 |
| His44 | 8.1 ± 0.2 | 8.1 ± 0.2 | N.D. | 24.5 ± 1.4 | 18.9 ± 1.3 | 18.8 ± 2.1 |
| Gln131 | 8.2 ± 0.2 | 7.9 ± 0.3 | N.D. | 17.3 ± 1.4* | 12.8 ± 1.1* | 13.7 ± 1.5 |
| Met149 | N.D. | N.D. | N.D. | N.D. | N.D. | 2.6 ± 0.4* |
| Ser168 | 8.1 ± 0.2 | 8.0 ± 0.2 | N.D. | 18.3 ± 1.0* | 13.9 ± 0.8* | 14.4 ± 0.9 |
| Leu260 | 8.2 ± 0.1 | 8.2 ± 0.1 | N.D. | 27.8 ± 1.2 | 21.3 ± 1.0 | 19.0 ± 1.9 |
| Thr316 | 7.8 ± 0.2 | 7.7 ± 0.5 | N.D. | 12.4 ± 1.0* | 7.3 ± 0.9* | 11.9 ± 1.9* |
| Cys333 | 7.8 ± 0.3 | 7.8 ± 0.2 | N.D. | 23.6 ± 2.4 | 14.6 ± 1.1* | 15.0 ± 2.4 |
| Gln421 | 7.9 ± 0.3 | 7.9 ± 0.3 | N.D. | 15.6 ± 1.7* | 13.6 ± 1.3* | 16.8 ± 7.8 |
N.D., data unable to be experimentally defined or with incomplete curves.
*
Statistically significant at p < 0.05.
a
Response at 10−6 M oxyntomodulin.