Publication
Title
Dipeptidyl peptidase 4 as a therapeutic target in ischemia/reperfusion injury
Author
Abstract
Dipeptidyl peptidase 4 (DPP4, DPPIV, CD26, EC 3.4.14.5) was discovered more than four decades ago as a serine protease that cleaves off N-terminal dipeptides from peptide substrates. The development of potent DPP4 inhibitors during the past two decades has led to the identification of DPP4 as a target in the treatment of type 2 diabetes. The favorable effect of DPP4 inhibitors is based on prevention of the in vivo inactivation of the incretin hormone, glucagon-like peptide-1 (GLP-1) by DPP4. Apart from GLP-1, a number of other biologically active peptides are truncated by DPP4. For these peptides, the physiological relevance of their truncation has yet to be fully elucidated. Within the last 10 years, DPP4 inhibitors have been employed in several animal models of lung and heart disease, in which injury was induced by an ischemic insult followed by subsequent reperfusion. In this review, we present a state-of-the-art of the ischemia/reperfusion injury (IRI)-related pharmacological actions of DPP4 substrates, including GLP-1, stromal cell-derived factor-1 alpha and vasoactive intestinal peptide. Furthermore, we discuss the large body of experimental work that now provides compelling evidence for the advantageous impact of DPP4 targeting in IRI. However, possible risks as well as underlying mechanisms are yet to be elucidated before translating these promising treatment strategies into clinical practice. Abbreviations BM, bone marrow; BNP, brain natriuretic peptide; EC, endothelial cell; ERK, extracellular signal regulated kinase; GLP-1, glucagon-like peptide-1; GSK3β, glycogen synthase kinase-β; GLUT, glucose transporter; HIF-1, hypoxia-inducible factor-1; IRI, ischemia/reperfusion injury; MI, myocardial infarction; MMP, matrix metalloproteinase; NPY, neuropeptide Y; PI3K, phosphatidylinositol-3-OH kinase; SDF-1α, stromal cell-derived factor-1 alpha; Tx, transplantation; VIP, vasoactive intestinal peptide
Language
English
Source (journal)
Pharmacology and therapeutics. - Oxford
Publication
Oxford : 2012
ISSN
0163-7258
Volume/pages
136:3(2012), p. 267-282
ISI
000311022900001
Full text (Publisher's DOI)
Full text (publisher's version - intranet only)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 03.08.2012
Last edited 04.10.2017
To cite this reference