title: Vildagliptin reduces cardiac ischemic-reperfusion injury in obese orchiectomized rats.
abstract: Obesity and testosterone deprivation are associated with coronary artery disease. Testosterone and vildagliptin (dipeptidyl peptidase-4 inhibitors) exert cardioprotection during ischemic-reperfusion (I/R) injury. However, the effect of these drugs on I/R heart in a testosterone-deprived, obese, insulin-resistant model is unclear. This study investigated the effects of testosterone and vildagliptin on cardiac function, arrhythmias and the infarct size in I/R heart of testosterone-deprived rats with obese insulin resistance. Orchiectomized (O) or sham operated (S) male Wistar rats were divided into 2 groups to receive normal diet (ND) or high-fat diet (HFD) for 12 weeks. Orchiectomized rats in each diet were divided to receive testosterone (2 mg/kg), vildagliptin (3 mg/kg) or the vehicle daily for 4 weeks. Then, I/R was performed by a 30-min left anterior descending coronary artery ligation, followed by a 120-min reperfusion. LV function, arrhythmia scores, infarct size and cardiac mitochondrial function were determined. HFD groups developed insulin resistance at week 12. At week 16, cardiac function was impaired in NDO, HFO and HFS rats, but was restored in all testosterone- and vildagliptin-treated rats. During I/R injury, arrhythmia scores, infarct size and cardiac mitochondrial dysfunction were prominently increased in NDO, HFO and HFS rats, compared with those in NDS rats. Treatment with either testosterone or vildagliptin similarly attenuated these impairments during I/R injury. These finding suggest that both testosterone replacement and vildagliptin share similar efficacy for cardioprotection during I/R injury by decreasing the infarct size and attenuating cardiac mitochondrial dysfunction caused by I/R injury in testosterone-deprived rats with obese insulin resistance.
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand.
authors.forename: Wanpitak
authors.initials: W
authors.lastname: Pongkan
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Hiranya
authors.initials: H
authors.lastname: Pintana
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand.
authors.forename: Thidarat
authors.initials: T
authors.lastname: Jaiwongkam
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand.
authors.forename: Sasiwan
authors.initials: S
authors.lastname: Kredphoo
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand.
authors.forename: Sivaporn
authors.initials: S
authors.lastname: Sivasinprasasn
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Department of Oral Biology and Diagnostic ScienceFaculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Siriporn C
authors.initials: SC
authors.lastname: Chattipakorn
authors.affiliation: Cardiac Electrophysiology Research and Training CenterFaculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Cardiac Electrophysiology UnitDepartment of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Center of Excellence in Cardiac Electrophysiology ResearchChiang Mai University, Chiang Mai, Thailand nchattip@gmail.com.
authors.forename: Nipon
authors.initials: N
authors.lastname: Chattipakorn
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D059305:Diet, High-Fat; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007333:Insulin Resistance; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology; D009570:Nitriles / Q000494:pharmacology*; D009765:Obesity / Q000503:physiopathology*; D009919:Orchiectomy; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D000077597:Vildagliptin
chemical_list: D000728:Androgens; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D013739:Testosterone; D000077597:Vildagliptin; D000218:Adamantane
keywords: cardiac mitochondrial function; dipeptidyl peptidase-4 inhibitors; ischemia–reperfusion; obese testosterone deprivation