Table 2. Quantification of Biased Agonism (ΔΔlog(τ/KA)) on GLP-1Ra.
ligand | cAMP:β-arrestin 2 | cAMP:calcium mobilization | cAMP:internalization | calcium mobilization:β-arrestin 2 | calcium mobilization:internalization | β-arrestin 2:internalization |
---|---|---|---|---|---|---|
GLP-1 | 0.00 ± 0.03 | 0.00 ± 0.05 | 0.00 ± 0.05 | 0.00 ± 0.06 | 0.00 ± 0.07 | 0.00 ± 0.05 |
GLP-1 Val8 | 0.10 ± 0.05 | –0.14 ± 0.05 | 0.65 ± 0.04**** | 0.24 ± 0.07 | 0.79 ± 0.06**** | 0.55 ± 0.06**** |
ΔΔlog(τ/KA) values determined for GLP-1 and GLP-1 Val8 across different functional outcomes. Data represent the mean ± s.e.m. of 18 independent experiments performed in duplicate for cAMP production and β-arrestin 2 recruitment, 4 independent experiments in duplicate for calcium mobilization, and 6 independent experiments performed in duplicate and triplicate for internalization. Statistical significance was assessed using a repeated measures two-way ANOVA (****P < 0.0001; between GLP-1 and GLP-1 Val8).