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Briefly, while the extracellular domain (ECD) of GLP-1R, which is responsible for ligand recognition and specificity, engages the C-terminus of the GLP-1, the interhelical transmembrane crevice of the GLP-1R helps in docking of the N-terminus of the GLP-1, triggering downstream signaling ( FIGURE 2 However, the naturally secreted GLP-1 is quickly hydrolyzed and rendered inactive by dipeptidyl peptidase-4 (DPP-4), a transmembrane amino peptidase