title: Kinetic study of the processing by dipeptidyl-peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion.
abstract: Dipeptidyl-peptidase IV (DPPIV/CD26) metabolizes neuropeptides regulating insulin secretion. We studied the in vitro steady-state kinetics of DPPIV/CD26-mediated truncation of vasoactive intestinal peptide (VIP), pituitary adenylyl 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 both PACAP38 binding and turnover. Therefore, residues remote from the scissile bond can modulate DPPIV/CD26 substrate selectivity as well as residues flanking it.
authors.affiliation: Laboratory of Medical Biochemistry, University of Antwerp, Belgium. lambeir@uia.ua.ac.be
authors.forename: A M
authors.initials: AM
authors.lastname: Lambeir
authors.forename: C
authors.initials: C
authors.lastname: Durinx
authors.forename: P
authors.initials: P
authors.lastname: Proost
authors.forename: J
authors.initials: J
authors.lastname: Van Damme
authors.forename: S
authors.initials: S
authors.lastname: Scharpé
authors.forename: I
authors.initials: I
authors.lastname: De Meester
mesh_terms: D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D019886:Gastrin-Releasing Peptide / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007700:Kinetics; D013058:Mass Spectrometry; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D013379:Substrate Specificity; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: C495401:ADCYAP1 protein, human; D007328:Insulin; D009478:Neuropeptide Y; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide; D019886:Gastrin-Releasing Peptide; D018819:Dipeptidyl Peptidase 4