DPPIV inhibition : Promising therapy for the treatment of type 2 diabetes

Publisher Summary Dipeptidyl Peptidase IV (DPPIV) is a post-proline cleaving serine protease with a catalytic triad of Ser-Asp-His inversely oriented to classical serine proteases and with significant homology to other α, β-hydroxylases. DPPIV is expressed as a 110 kDa glycoprotein on the surface of cells of most tissues, including kidney, liver, intestine, placenta, prostate, skin, lymphocytes, and endothelial cells. DPPIV is catalytically active as a dimer. Proteolytic cleavage of DPPIV from cell surfaces results in a soluble circulating form with a monomeric mass of approximately 100 kDa. In addition to cleaving glucagon-like peptide-1, DPPIV may play a role in the cleavage of other substrates with accessible amino-terminal Xaa-Pro- or Xaa-Ala-dipeptide sequences, resulting in their inactivation or alteration in their biological activities. Potential DPPIV substrates include growth hormone releasing hormone; glucose-dependent insulinotropic polypeptide; pituitary adenylate cyclase-activating polypeptide 38; substance P; bradykinin; gastrin releasing peptide; neuropeptide Y; peptide YY; certain chemokines, such as regulated on activation normal T cell expressed and secreted; stromal cell-derived factor; and eotaxin and macrophage-derived chemokines.