TABLE 3.
Comparison of GIP(1-42), GIP(1-30)NH2 and Tirzepatide efficacy (log (τ/KA)) at human WT and E354Q GIP receptors, when normalized to GIP(1-42) at the WT GIP receptor.
| GIP receptor | Peptide | Log (τ/KA) | ||||
|---|---|---|---|---|---|---|
| cAMP | IP1 | pAKT | pERK1/2 | pCREB | ||
| WT | GIP(1-42) | 10.6 ± 0.04 | 8.35 ± 0.07 | 8.67 ± 0.11 | 9.01 ± 0.18 | 9.57 ± 0.22 |
| 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 ± 0.11 | 7.51 ± 0.06 | 7.88 ± 0.10 | 8.76 ± 0.08 | |
| E354Q | GIP(1-42) | 10.7 ± 0.20 | 9.02 ± 0.16* | 8.76 ± 0.11 | 9.05 ± 0.15 | 10.1 ± 0.16 |
| GIP(1-30)NH2 | 10.8 ± 0.06 | 8.86 ± 0.05* | 8.77 ± 0.09 | 9.28 ± 0.30 | 11.1 ± 0.37* | |
| Tirzepatide | 9.75 ± 0.11 | 7.80 ± 0.15 | 7.44 ± 0.11 | 7.75 ± 0.05 | 8.83 ± 0.05 | |
Data normalized to the maximal response produced by GIP(1-42) at the WT GIP, receptor, for both the WT, and E354Q GIP, receptor. The data was then fitted to the Operational model. Data are mean ± s. e.m of the combined data from 3 (pAKT, pERK1/2, pCREB) or 5 (cAMP, IP1) independent experiments. *p < 0.05 by unpaired Student’s t-test comparing the log ((τ/KA) of the same peptide at the WT, and E354Q GIP, receptors for each signaling pathway.