TABLE 3

Effects of human GLP-1 receptor mutation on agonist signaling

All mutants were analyzed with an operational model of agonism (eq. 2) to determine logτ values. All logτ values were then corrected to Bmax values determined from homologous competition binding between [125I]exendin(9-39) and unlabeled exendin(9-39) (logτc). Values are expressed as mean ± S.E.M. of four to six independent experiments, conducted in duplicate. Data were analyzed with one-way analysis of variance and Dunnett’s post-test.

cAMP Accumulation (Logτc)pERK1/2 (Logτc)iCa2+ Mobilization (Logτc)
GLP-1 
(7-36)NH2Exendin-4Oxynto-
modulinGLP-1 
(7-36)NH2Exendin-4Oxynto-
modulinGLP-1 
(7-36)NH2Exendin-4Oxynto-modulin
Wild-type1.22 ± 0.111.33 ± 0.110.92 ± 0.16−0.08 ± 0.03−0.09 ± 0.03−0.07 ± 0.03−0.30 ± 0.00−0.31 ± 0.03−0.31 ± 0.02
R2.60190Aa0.53 ± 0.07*0.80 ± 0.08*1.56 ± 0.09*–0.39 ± 0.08*0.51 ± 0.12*0.03 ± 0.07−0.66 ± 0.16−0.72 ± 0.110.11 ± 0.05*
N3.43240Aa0.55 ± 0.12*1.46 ± 0.150.89 ± 0.100.01 ± 0.040.19 ± 0.05*0.04 ± 0.02−0.76 ± 0.16–0.96 ± 0.10*−0.29 ± 0.04
Q7.49394Aa0.86 ± 0.111.16 ± 0.150.41 ± 0.05*–0.54 ± 0.05*−0.29 ± 0.05−0.20 ± 0.01–1.12 ± 0.13*–1.13 ± 0.34*N.D.
N3.43240A/Q7.49394A0.52 ± 0.12*1.07 ± 0.110.71 ± 0.12–0.56 ± 0.04*–0.43 ± 0.07*−0.09 ± 0.031.11 ± 0.19*N.D.N.D.
N3.43240Q1.09 ± 0.131.15 ± 0.170.74 ± 0.07−0.09 ± 0.04−0.05 ± 0.03−0.27 ± 0.04–0.80 ± 0.05*−0.71 ± 0.10N.D.
Q7.49394N0.91 ± 0.141.30 ± 0.130.45 ± 0.09*−0.09 ± 0.04−0.05 ± 0.03−0.10 ± 0.03−0.70 ± 0.04−0.67 ± 0.03–0.59 ± 0.07*
N3.43240Q/Q7.49394N0.75 ± 0.160.87 ± 0.150.44 ± 0.10*−0.06 ± 0.04−0.00 ± 0.03–0.44 ± 0.06*–1.15 ± 0.10*–1.00 ± 0.14*N.D.
E6.53364A0.56 ± 0.07*0.85 ± 0.06*1.10 ± 0.06−0.35 ± 0.08−0.37 ± 0.09−0.11 ± 0.07−0.38 ± 0.13−0.68 ± 0.040.04 ± 0.05
H6.52363Aa–0.51 ± 0.11*–0.31 ± 0.06*–0.26 ± 0.06*–0.81 ± 0.15*–0.67 ± 0.07*−0.19 ± 0.08–1.09 ± 0.13*–1.33 ± 0.22*−0.23 ± 0.27
  • N.D., no data.

  • * Statistically significant at p < 0.05, one-way analysis of variance and Dunnett’s post-test in comparison with wild-type control. For easy comparison between effects of different ligands and mutants, these are also highlighted in bold.

  • a Data obtained from Wootten et al. (2013a).