TABLE 1

Differential effects of peptide/small molecule agonists of the human GLP-1R in cAMP accumulation, iCa2+ mobilization, pERK1/2, and β-arrestin1 and β-arrestin2 recruitment in Flp-In-CHO cells stably expressing the human GLP-1R

pEC50 values are the negative logarithm of the concentration of agonist that produces half the maximal response. Emax represents the maximal response normalized to that of GLP-1(7–36)NH2. All values are mean ± S.E.M. of three to five independent experiments conducted in duplicate.

Signaling PathwayLigand
GLP-1(7–36)NH2BMS21Boc5TT15BETPCompound 2
cAMPpEC5010.4 ± 0.16.7 ± 0.66.7 ± 0.26.5 ± 0.25.2 ± 0.25.6 ± 0.1
Emax100 ± 2132 ± 630 ± 246 ± 317 ± 281 ± 4
pERK1/2pEC507.9 ± 0.16.8 ± 0.16.5 ± 0.16.7 ± 0.3NR6.2 ± 0.1
Emax100 ± 546 ± 219 ± 112 ±NR18 ± 1
iCa2+pEC507.9 ± 0.17.0 ± 0.36.0 ± 0.3NR5 ± 0.3NR
Emax100 ± 517 ± 322 ± 2NR42 ± 10NR
β-Arr1pEC507.7 ± 0.1NRNRND5.0 ± 0.25.0 ± 0.2
Emax100 ± 6NRNRND40 ± 730 ± 5
β-Arr2pEC507.4 ± 0.1NRNRND5.0 ± 0.34.8 ± 0.2
Emax100 ± 5NRNRND63 ± 1551 ± 0.2
  • β-Arr, beta arrestin; BETP, 4-(3-benzyloxyphenyl)-2-ethylsulfinyl-6-(trifluoromethyl)pyrimidine; Boc5, 1,3-bis [[4-(tert-butoxy-carbonylamino)benzoyl]amino]-2,4-bis[3-methoxy-4-(thiophene-2-carbonyloxy)-phenyl]cyclobutane-1,3-dicarboxylic acid; Compound 2, 6.7-dichloro-2-methylsulfonyl-3-tert-butylaminoquinoxaline; ERK1/2, extracellular signal-related kinases 1 and 2; iCa2+, intracellular calcium; ND, not detected; NR, no response; TT15, (2S)-2-[[(8S)-7-benzoyl-3-[4-[(3,4-dichlorophenyl)methoxy]phenyl]-2-oxo-1,6,8,9-tetrahydropyrido[4,3-g][1,4]benzoxazine-8-carbonyl]amino]-3-[4-(4-cyanophenyl)phenyl]propanoic acid.