Table 2.
Parameter estimates for responses in beta cell models. Mean ± SEM for potency and efficacy estimates from Fig. 4. Emax values are reported as in the figure, i.e. as a % of forskolin response for INS-1 cAMP results, % remaining surface receptor for GLP-1R downregulation assay, and as fold change response versus 11 mM glucose for the insulin secretion assay. Statistical comparisons are by one-way randomised block ANOVA with Tukey’s test. * p < 0.05 versus exendin-4; # p < 0.05 exendin-F1 versus P5. n.c. = not calculable.
| Exendin-4 |
Exendin-F1 |
P5 |
||||
|---|---|---|---|---|---|---|
| Assay and cell model | pEC50 (M) | Emax | pEC50 (M) | Emax | pEC50 (M) | Emax |
| cAMP (INS-1 832/3, wild-type) | 9.6 ± 0.1 | 76 ± 11 | 8.6 ± 0.2 * | 74 ± 12 | 8.1 ± 0.2 *,# | 91 ± 13 *,# |
| cAMP (INS-1 832/3, GLP-1R KO) | n.c. | n.c. | n.c. | n.c. | n.c. | n.c. |
| cAMP (INS-1 832/3, GIPR KO) | 9.8 ± 0.1 | 76 ± 13 | 8.8 ± 0.2 * | 80 ± 14 | 8.3 ± 0.2 *,# | 93 ± 15 *,# |
| GLP-1R downregulation (INS-1-SNAP-GLP-1R) | 9.2 ± 0.2 | 6 ± 2 | 7.7 ± 0.2 * | 39 ± 5 * | 6.6 ± 0.2 *,# | 6 ± 3 # |
| Insulin secretion (INS-1 832/3) | 10.3 ± 0.1 | 2.7 ± 0.3 | 9.4 ± 0.1 * | 4.3 ± 0.3 * | 9.1 ± 0.3 * | 2.5 ± 0.4 # |