title: Dipeptidyl peptidase 4 inhibition may facilitate healing of chronic foot ulcers in patients with type 2 diabetes.
abstract: The pathophysiology of chronic diabetic ulcers is complex and still incompletely understood, both micro- and macroangiopathy strongly contribute to the development and delayed healing of diabetic wounds, through an impaired tissue feeding and response to ischemia. With adequate treatment, some ulcers may last only weeks; however, many ulcers are difficult to treat and may last months, in certain cases years; 19-35% of ulcers are reported as nonhealing. As no efficient therapy is available, it is a high priority to develop new strategies for treatment of this devastating complication. Because experimental and pathological studies suggest that incretin hormone glucagon-like peptide-1 may improves VEGF generation and promote the upregulation of HIF-1α through a reduction of oxidative stress, the study evaluated the effect of the augmentation of GLP-1, by inhibitors of the dipeptidyl peptidase-4, such as vildagliptin, on angiogenesis process and wound healing in diabetic chronic ulcers. Although elucidation of the pathophysiologic importance of these aspects awaits further confirmations, the present study evidences an additional aspect of how DPP-4 inhibition might contribute to improved ulcer outcome.
authors.affiliation: Department of Geriatrics and Metabolic Diseases, Second University of Naples, 80138 Naples, Italy. raffaele.marfella@unina2.it
authors.forename: Raffaele
authors.initials: R
authors.lastname: Marfella
authors.forename: Ferdinando Carlo
authors.initials: FC
authors.lastname: Sasso
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Rizzo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Paolisso
authors.forename: Michelangela
authors.initials: M
authors.lastname: Barbieri
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Padovano
authors.forename: Ornella
authors.initials: O
authors.lastname: Carbonara
authors.forename: Pasquale
authors.initials: P
authors.lastname: Gualdiero
authors.forename: Pasquale
authors.initials: P
authors.lastname: Petronella
authors.forename: Franca
authors.initials: F
authors.lastname: Ferraraccio
authors.forename: Antonello
authors.initials: A
authors.lastname: Petrella
authors.forename: Raffaele
authors.initials: R
authors.lastname: Canonico
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Campitiello
authors.forename: Angela
authors.initials: A
authors.lastname: Della Corte
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paolisso
authors.forename: Silvestro
authors.initials: S
authors.lastname: Canonico
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D002196:Capillaries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D017719:Diabetic Foot / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007558:Italy; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009570:Nitriles / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011759:Pyrrolidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D000077597:Vildagliptin; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009570:Nitriles; D011759:Pyrrolidines; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D046988:Proteasome Endopeptidase Complex; D000077597:Vildagliptin; D000218:Adamantane