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Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus

Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I(to)) remodeling in ventricular myocytes and the plas...

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Autores principales: Xiang, Yu-luan, He, Li, Xiao, Jun, Xia, Shuang, Deng, Song-bai, Xiu, Yun, She, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sociedade Brasileira de Medicina Tropical 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854190/
https://www.ncbi.nlm.nih.gov/pubmed/22331134
http://dx.doi.org/10.1590/S0100-879X2012007500019
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author Xiang, Yu-luan
He, Li
Xiao, Jun
Xia, Shuang
Deng, Song-bai
Xiu, Yun
She, Qiang
author_facet Xiang, Yu-luan
He, Li
Xiao, Jun
Xia, Shuang
Deng, Song-bai
Xiu, Yun
She, Qiang
author_sort Xiang, Yu-luan
collection PubMed
description Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I(to)) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg(−1)·day(−1)). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of I(to) was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated I(to) reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced I(to) of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM.
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spelling pubmed-38541902013-12-16 Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus Xiang, Yu-luan He, Li Xiao, Jun Xia, Shuang Deng, Song-bai Xiu, Yun She, Qiang Braz J Med Biol Res Short Communication Cardiovascular complications are a leading cause of mortality in patients with diabetes mellitus (DM). The present study was designed to investigate the effects of trimetazidine (TMZ), an anti-angina drug, on transient outward potassium current (I(to)) remodeling in ventricular myocytes and the plasma contents of free fatty acid (FFA) and glucose in DM. Sprague-Dawley rats, 8 weeks old and weighing 200-250 g, were randomly divided into three groups of 20 animals each. The control group was injected with vehicle (1 mM citrate buffer), the DM group was injected with 65 mg/kg streptozotocin (STZ) for induction of type 1 DM, and the DM+TMZ group was injected with the same dose of STZ followed by a 4-week treatment with TMZ (60 mg·kg(−1)·day(−1)). All animals were then euthanized and their hearts excised and subjected to electrophysiological measurements or gene expression analyses. TMZ exposure significantly reversed the increased plasma FFA level in diabetic rats, but failed to change the plasma glucose level. The amplitude of I(to) was significantly decreased in left ventricular myocytes from diabetic rats relative to control animals (6.25 ± 1.45 vs 20.72 ± 2.93 pA/pF at +40 mV). The DM-associated I(to) reduction was attenuated by TMZ. Moreover, TMZ treatment reversed the increased expression of the channel-forming alpha subunit Kv1.4 and the decreased expression of Kv4.2 and Kv4.3 in diabetic rat hearts. These data demonstrate that TMZ can normalize, or partially normalize, the increased plasma FFA content, the reduced I(to) of ventricular myocytes, and the altered expression Kv1.4, Kv4.2, and Kv4.3 in type 1 DM. Sociedade Brasileira de Medicina Tropical 2012-02-17 /pmc/articles/PMC3854190/ /pubmed/22331134 http://dx.doi.org/10.1590/S0100-879X2012007500019 Text en http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Communication
Xiang, Yu-luan
He, Li
Xiao, Jun
Xia, Shuang
Deng, Song-bai
Xiu, Yun
She, Qiang
Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus
title Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus
title_full Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus
title_fullStr Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus
title_full_unstemmed Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus
title_short Effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus
title_sort effect of trimetazidine treatment on the transient outward potassium current of the left ventricular myocytes of rats with streptozotocin-induced type 1 diabetes mellitus
topic Short Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3854190/
https://www.ncbi.nlm.nih.gov/pubmed/22331134
http://dx.doi.org/10.1590/S0100-879X2012007500019
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