TABLE 2.
Summary of peptide efficacy (log ((τ/KA)) values at WT and E354Q GIP receptors in transfected Cos7 cells.
| GIP receptor | Peptide | Log (τ/KA) | ||||
|---|---|---|---|---|---|---|
| cAMP | IP1 | pAKT | pERK1/2 | pCREB | ||
| WT | GIP(1-42) | 10.6 ± 0.09 | 8.35 ± 0.07^ | 8.67 ± 0.11^ | 9.01 ± 0.18^ | 9.57 ± 0.23^ |
| GIP(1-30)NH2 | 10.7 ± 0.09 | 8.53 ± 0.08^ | 8.76 ± 0.05^ | 8.96 ± 0.13^ | 9.80 ± 0.20^ | |
| Tirzepatide | 9.85 ± 0.12& | 7.48 ± 0.12&^ | 7.51 ± 0.06&^ | 7.88 ± 0.10&^ | 8.76 ± 0.08&^ | |
| E354Q | GIP(1-42) | 10.7 ± 0.18 | 9.24 ± 0.10*^ | 8.98 ± 0.02^ | 9.22 ± 0.14^ | 10.2 ± 0.24 |
| GIP(1-30)NH2 | 10.9 ± 0.03* | 9.10 ± 0.03*^ | 8.99 ± 0.26^ | 9.45 ± 0.26 ^ | 11.3 ± 0.41* | |
| Tirzepatide | 9.83 ± 0.06& | 8.07 ± 0.14*&^ | 7.66 ± 0.14&^ | 7.92 ± 0.08&^ | 8.94 ± 0.13&^ | |
Data are mean ± s. e.m of the combined data from 3 (pAKT, pERK1/2, pCREB) or 5 (cAMP, IP1) independent experiments. The operational model was performed on data normalized to the maximal response produced by GIP(1-42) for each receptor. *p < 0.05 by unpaired Student’s t-test comparing the log ((τ/KA) of the peptide at the E354Q GIP, receptor with the WT GIP, receptor for each signaling assay. & p < 0.05 by one-way ANOVA, with Dunnett’s post hoc test comparing the log (τ/KA) for each peptide to GIP(1-42) at that receptor. ^p < 0.05 by one-way ANOVA, with Dunnett’s post hoc test comparing the log (τ/KA) for each signaling pathway to cAMP, for each peptide at that receptor.