Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats

Background: Obese-insulin resistance caused by long-term high-fat diet (HFD) consumption is associated with left ventricular (LV) dysfunction and increased risk of myocardial infarction. Metformin and vildagliptin have been shown to exert cardioprotective effects. However, the effect of these drugs...

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Main Authors: Nattayaporn Apaijai, Kroekkiat Chinda, Siripong Palee, Siriporn Chattipakorn, Nipon Chattipakorn
Format: Journal
Published: 2018
Online Access:https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84904540452&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/45012
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spelling th-cmuir.6653943832-450122018-01-24T06:04:07Z Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats Nattayaporn Apaijai Kroekkiat Chinda Siripong Palee Siriporn Chattipakorn Nipon Chattipakorn Background: Obese-insulin resistance caused by long-term high-fat diet (HFD) consumption is associated with left ventricular (LV) dysfunction and increased risk of myocardial infarction. Metformin and vildagliptin have been shown to exert cardioprotective effects. However, the effect of these drugs on the hearts under obese-insulin resistance with ischemia-reperfusion (I/R) injury is unclear. We hypothesized that combined vildagliptin and metformin provide better protective effects against I/R injury than monotherapy in obese-insulin resistant rats. Methodology: Male Wistar rats were fed either HFD or normal diet. Rats in each diet group were divided into 4 subgroups to receive vildagliptin, metformin, combined vildagliptin and metformin, or saline for 21 days. Ischemia due to left anterior descending artery ligation was allowed for 30-min, followed by 120-min reperfusion. Metabolic parameters, heart rate variability (HRV), LV function, infarct size, mitochondrial function, calcium transient, Bax and Bcl-2, and Connexin 43 (Cx43) were determined. Rats developed insulin resistance after 12 weeks of HFD consumption. Vildagliptin, metformin, and combined drugs improved metabolic parameters, HRV, and LV function. During I/R, all treatments improved LV function, reduced infarct size and Bax, increased Bcl-2, and improved mitochondrial function in HFD rats. However, only combined drugs delayed the time to the first VT/VF onset, reduced arrhythmia score and mortality rate, and increased p-Cx43 in HFD rats. Conclusion: Although both vildagliptin and metformin improved insulin resistance and attenuate myocardial injury caused by I/R, combined drugs provided better outcomes than single therapy by reducing arrhythmia score and mortality rate. © 2014 Apaijai et al. 2018-01-24T06:04:07Z 2018-01-24T06:04:07Z 2014-07-18 Journal 19326203 2-s2.0-84904540452 10.1371/journal.pone.0102374 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84904540452&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/45012
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
description Background: Obese-insulin resistance caused by long-term high-fat diet (HFD) consumption is associated with left ventricular (LV) dysfunction and increased risk of myocardial infarction. Metformin and vildagliptin have been shown to exert cardioprotective effects. However, the effect of these drugs on the hearts under obese-insulin resistance with ischemia-reperfusion (I/R) injury is unclear. We hypothesized that combined vildagliptin and metformin provide better protective effects against I/R injury than monotherapy in obese-insulin resistant rats. Methodology: Male Wistar rats were fed either HFD or normal diet. Rats in each diet group were divided into 4 subgroups to receive vildagliptin, metformin, combined vildagliptin and metformin, or saline for 21 days. Ischemia due to left anterior descending artery ligation was allowed for 30-min, followed by 120-min reperfusion. Metabolic parameters, heart rate variability (HRV), LV function, infarct size, mitochondrial function, calcium transient, Bax and Bcl-2, and Connexin 43 (Cx43) were determined. Rats developed insulin resistance after 12 weeks of HFD consumption. Vildagliptin, metformin, and combined drugs improved metabolic parameters, HRV, and LV function. During I/R, all treatments improved LV function, reduced infarct size and Bax, increased Bcl-2, and improved mitochondrial function in HFD rats. However, only combined drugs delayed the time to the first VT/VF onset, reduced arrhythmia score and mortality rate, and increased p-Cx43 in HFD rats. Conclusion: Although both vildagliptin and metformin improved insulin resistance and attenuate myocardial injury caused by I/R, combined drugs provided better outcomes than single therapy by reducing arrhythmia score and mortality rate. © 2014 Apaijai et al.
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author Nattayaporn Apaijai
Kroekkiat Chinda
Siripong Palee
Siriporn Chattipakorn
Nipon Chattipakorn
spellingShingle Nattayaporn Apaijai
Kroekkiat Chinda
Siripong Palee
Siriporn Chattipakorn
Nipon Chattipakorn
Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats
author_facet Nattayaporn Apaijai
Kroekkiat Chinda
Siripong Palee
Siriporn Chattipakorn
Nipon Chattipakorn
author_sort Nattayaporn Apaijai
title Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats
title_short Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats
title_full Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats
title_fullStr Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats
title_full_unstemmed Combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats
title_sort combined vildagliptin and metformin exert better cardioprotection than monotherapy against ischemia-reperfusion injury in obese-insulin resistant rats
publishDate 2018
url https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84904540452&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/45012
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