Table 2.

Stimulus bias exhibited by α- and α/β-peptides P1 – P9 relative to the reference agonist GLP-1.

Δlog(τ/KA)
	Ca2+ vs cAMP	pERK1/2 vs cAMP	βArr1 vs cAMP	βArr2 vs cAMP	βArr1 vs Ca2+	βArr2 vs Ca2+	βArr1 vs pERK1/2	βArr2 vs pERK1/2
GLP-1	0.0 ± 0.1	0.0 ± 0.2	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.1	0.0 ± 0.2	0.0 ± 0.2
P1	0.4 ± 0.1	0.5 ± 0.2	0.4 ± 0.1	0.5 ± 0.2	−0.1 ± 0.2	−0.2 ± 0.2	0.0 ± 0.2	−0.1 ± 0.3
P2	0.4 ± 0.1	0.8 ± 0.2	−0.3 ± 0.4	−0.3 ± 0.3	−0.7 ± 0.5	−0.7* ± 0.2	−1.0 ± 0.5	−1.0* ± 0.3
P3	−0.6* ± 0.1	0.9* ± 0.2	0.8* ± 0.2	0.5 ± 0.3	1.4* ± 0.2	0.9* ± 0.1	−0.1 ± 0.3	−0.6 ± 0.2
P4	−0.2 ± 0.2	1.6* ± 0.3	N.D.	N.D.	N.D.	N.D.	N.D.	N.D.
P5	−0.4 ± 0.2	0.3 ± 0.3	0.5 ± 0.1	−0.3 ± 0.2	0.7 ± 0.2	−0.1 ± 0.2	0.1 ± 0.3	−0.8 ± 0.3
P6	−0.1 ± 0.2	0.1 ± 0.2	0.4 ± 0.1	−0.1 ± 0.2	0.9* ± 0.2	0.0 ± 0.2	0.5 ± 0.3	−0.3 ± 0.2
P7	−0.6* ± 0.1	0.3 ± 0.2	−0.1 ± 0.3	−0.5 ± 0.4	0.4 ± 0.3	−0.1 ± 0.1	−0.4 ± 0.4	−0.9* ± 0.3
P8	−0.6* ± 0.1	0.7 ± 0.3	0.8* ± 0.1	N.D.	1.4* ± 0.1	N.D.	0.0 ± 0.3	N.D.
P9	N.D.	1.2* ± 0.3	1.1* ± 0.4	N.D.	N.D.	N.D.	−0.1 ± 0.5	N.D.

Stimulus bias exhibited by P1 – P9 relative to GLP-1in Ca²⁺ mobilization relative to cAMP accumulation, ERK1/2 phosphorylation relative to cAMP accumulation, β-Arrestin-1 recruitment relative to cAMP accumulation, β-Arrestin-2 recruitment relative to cAMP accumulation, β-Arrestin-1 recruitment relative to Ca²⁺ mobilization, β-Arrestin-2 recruitment relative to Ca²⁺ mobilization, β-Arrestin-1 recruitment relative to ERK1/2 phosphorylation, and β-Arrestin-2 recruitment relative to ERK1/2 phosphorylation. Changes in log (τ/K_A) were calculated to provide a measure of the degree of stimulus bias exhibited between different signaling pathways relative to that of the reference agonist GLP-1. Values are the mean ± SEM of three to four individual experiments, conducted in duplicate.

^*statistically significant difference from GLP-1 using one-way analysis of variance followed by Dunnett’s test.