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This mechanism of activation has two very important biochemical, pharmacological, and physiological consequences for the GLP-1R: a) The agonist-bound intermediate and fully active states of the receptor are separated from the inactive (agonist unbound, apo) state by a large energy barrier, meaning that GLP-1R has zero constitutive activity and the duration of its signaling through cAMP is completely dictated by the amount of time it is bound to the agonist

Lazzeri L, Di Giovanni A, Exacoustos C, Tosti C, Pinzauti S, Malzoni M, et al