{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:40:18Z","timestamp":1784180418145,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,6,12]],"date-time":"2013-06-12T00:00:00Z","timestamp":1370995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Long\u2010term high\u2010fat diet (<jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content>) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase\u20104 (<jats:styled-content style=\"fixed-case\">DPP<\/jats:styled-content>\u20104) inhibitors, vildagliptin and sitagliptin, are oral anti\u2010diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Male <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>istar rats weighing 180\u2013200\u2009g, were fed either a normal diet (20% energy from fat) or a <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content> (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>), sitagliptin (30\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup>) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (<jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content>), cardiac function and cardiac mitochondrial function were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Rats that received <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content> developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high\u2010density lipoprotein (<jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content>) level. Moreover, cardiac dysfunction, depressed <jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content>, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in <jats:styled-content style=\"fixed-case\">HFD<\/jats:styled-content> rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased <jats:styled-content style=\"fixed-case\">HDL<\/jats:styled-content> level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored <jats:styled-content style=\"fixed-case\">HRV<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin\u2010resistant rats.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.12176","type":"journal-article","created":{"date-parts":[[2013,3,15]],"date-time":"2013-03-15T01:32:46Z","timestamp":1363311166000},"page":"1048-1057","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["Effects of vildagliptin versus sitagliptin, on cardiac function, heart rate variability and mitochondrial function in obese insulin\u2010resistant 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