Fig. 1
From: DPP-4 inhibitors and GLP-1RAs: cardiovascular safety and benefits
Molecular basis of incretin axis: DPP-4 proteins consist of a short intracellular domain (6 amino acids), a transmembrane domain, and a large extracellular domain. The extracellular domain is responsible for the enzymatic cleavage of the substrates and binding to its ligands including fibronectin and ADA. DPP-4 inactivates GLP-1 by removing N-terminal dipeptide His7Ala8 from active form of GLP-1, which results in the loss of its affinity to GLP-1R. GLP-1R is a G-protein coupled receptor and its biding with active GLP-1 activates PI3K and PKA pathway by increasing intracellular cAMP concentration. DPP-4 dipeptidyl peptidase-4, sDPP-4 soluble DPP-4, AA amino acid, ADA adenosine deaminase, GLP-1 glucagon-like peptide-1, GLP-1R glucagon-like peptide-1 receptor, cAMP cyclic adenosine monophosphate, PKA protein kinase A, PI3K phosphoinositide 3-kinase