Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion

Dipeptidyl-peptidase IV (DPPIV/CD26) metabolizes neuropeptides regulating i nsulin secretion. We studied the in vitro steady-state kinetics of DPPIV/CD 26-mediated truncation of vasoactive intestinal peptide (VIP), pituitary ad enylyl cyclase-activating peptide (PACAP27 and PACAP38), gastrin-releasing peptide (GRP) and neuropeptide Y (NPY). DPPIV/CD26 sequentially cleaves off two dipeptides of VIP, PACAP27, PACAP38 and GRP. GRP situates between the best DPPIV/CD26 substrates reported, comparable to NPY. Surprisingly, the C -terminal extension of PACAP38, distant from the scissile bond, improves bo th PACAP38 binding and turnover. Therefore, residues remote from the scissi le bond can modulate DPPIV/CD26 substrate selectivity as well as residues f lanking it. (C) 2001 Federation of European Biochemical Societies. Publishe d by Elsevier Science B.V. All rights reserved.