Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction
© 2016 Society for Endocrinology. Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adve...
Saved in:
Main Authors: | , , , , |
---|---|
Format: | Journal |
Published: |
2017
|
Online Access: | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84977659591&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/42288 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Chiang Mai University |
id |
th-cmuir.6653943832-42288 |
---|---|
record_format |
dspace |
spelling |
th-cmuir.6653943832-422882017-09-28T04:26:19Z Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction Apaijai N. Inthachai T. Lekawanvijit S. Chattipakorn S. Chattipakorn N. © 2016 Society for Endocrinology. Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adverse remodeling after MI in obese-insulin-resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant rats with MI. Rats were fed either normal diet (ND) or highfat diet (HFD) for 12 weeks to induce obese-insulin resistance, followed by left anterior descending coronary artery ligation to induce MI. Then, rats in each dietary group were divided into five subgroups to receive vehicle, enalapril (10 mg/kg/day), metformin (30 mg/kg/day), DPP4 inhibitor vildagliptin (3 mg/kg/day), or combined metformin and vildagliptin for 8 weeks. Heart rate variability (HRV), LV function, pathological and biochemical studies for LV remodeling, and cardiomyocyte apoptosis were determined. Obese-insulin-resistant rats had severe insulin resistance and LV dysfunction. HFD rats had a higher mortality rate than ND rats, and all treatments reduced the mortality rate in obese-insulin-resistant rats. Although all drugs improved insulin resistance, HRV, LV function as well as reduced cardiac hypertrophy and fibrosis, vildagliptin effectively reduced cardiomyocyte cross-sectional areas more than enalapril and was related to markedly decreased ERK1/2 phosphorylation. In ND rats with MI, metformin neither improved LV ejection fraction nor reduced cardiac fibrosis. The infarct size and transforming growth factor-ß expression were not different among groups. In obese-insulin-resistant rats with chronic MI, DPP4 inhibitor vildagliptin exerts better cardioprotection than enalapril in attenuating adverse LV remodeling. 2017-09-28T04:26:19Z 2017-09-28T04:26:19Z 2016-01-01 Journal 00220795 2-s2.0-84977659591 10.1530/JOE-16-0096 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84977659591&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/42288 |
institution |
Chiang Mai University |
building |
Chiang Mai University Library |
country |
Thailand |
collection |
CMU Intellectual Repository |
description |
© 2016 Society for Endocrinology. Adverse cardiac remodeling after myocardial infarction (MI) leads to progressive heart failure. Obese-insulin resistance increases risks of MI and heart failure. Although dipeptidyl peptidase-4 (DPP4) inhibitor is known to exert cardioprotection, its effects on adverse remodeling after MI in obese-insulin-resistant rats are unclear. We hypothesized that DPP4 inhibitor reduces adverse left ventricular (LV) remodeling and LV dysfunction in obese-insulin-resistant rats with MI. Rats were fed either normal diet (ND) or highfat diet (HFD) for 12 weeks to induce obese-insulin resistance, followed by left anterior descending coronary artery ligation to induce MI. Then, rats in each dietary group were divided into five subgroups to receive vehicle, enalapril (10 mg/kg/day), metformin (30 mg/kg/day), DPP4 inhibitor vildagliptin (3 mg/kg/day), or combined metformin and vildagliptin for 8 weeks. Heart rate variability (HRV), LV function, pathological and biochemical studies for LV remodeling, and cardiomyocyte apoptosis were determined. Obese-insulin-resistant rats had severe insulin resistance and LV dysfunction. HFD rats had a higher mortality rate than ND rats, and all treatments reduced the mortality rate in obese-insulin-resistant rats. Although all drugs improved insulin resistance, HRV, LV function as well as reduced cardiac hypertrophy and fibrosis, vildagliptin effectively reduced cardiomyocyte cross-sectional areas more than enalapril and was related to markedly decreased ERK1/2 phosphorylation. In ND rats with MI, metformin neither improved LV ejection fraction nor reduced cardiac fibrosis. The infarct size and transforming growth factor-ß expression were not different among groups. In obese-insulin-resistant rats with chronic MI, DPP4 inhibitor vildagliptin exerts better cardioprotection than enalapril in attenuating adverse LV remodeling. |
format |
Journal |
author |
Apaijai N. Inthachai T. Lekawanvijit S. Chattipakorn S. Chattipakorn N. |
spellingShingle |
Apaijai N. Inthachai T. Lekawanvijit S. Chattipakorn S. Chattipakorn N. Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction |
author_facet |
Apaijai N. Inthachai T. Lekawanvijit S. Chattipakorn S. Chattipakorn N. |
author_sort |
Apaijai N. |
title |
Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction |
title_short |
Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction |
title_full |
Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction |
title_fullStr |
Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction |
title_full_unstemmed |
Effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction |
title_sort |
effects of dipeptidyl peptidase-4 inhibitor in insulin-resistant rats with myocardial infarction |
publishDate |
2017 |
url |
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84977659591&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/42288 |
_version_ |
1681422160866836480 |