Cargando…

Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach

The incidence and mortality of cardiovascular disease in diabetic patients are 2-3 times higher than those in non-diabetic patients. Abnormal function of the L-type calcium channel in myocardial tissue might result in multiple cardiac disorders such as a prolonged QT interval. Therefore, QT prolonga...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Hui, Wang, Cao, Lu, Yuan, Yan, Yan, Leng, Dongjing, Tian, Shanshan, Zheng, Dongjie, Wang, Zhiguo, Bai, Yunlong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300225/
https://www.ncbi.nlm.nih.gov/pubmed/32595491
http://dx.doi.org/10.3389/fphar.2020.00614
_version_ 1783547544289148928
author Wang, Hui
Wang, Cao
Lu, Yuan
Yan, Yan
Leng, Dongjing
Tian, Shanshan
Zheng, Dongjie
Wang, Zhiguo
Bai, Yunlong
author_facet Wang, Hui
Wang, Cao
Lu, Yuan
Yan, Yan
Leng, Dongjing
Tian, Shanshan
Zheng, Dongjie
Wang, Zhiguo
Bai, Yunlong
author_sort Wang, Hui
collection PubMed
description The incidence and mortality of cardiovascular disease in diabetic patients are 2-3 times higher than those in non-diabetic patients. Abnormal function of the L-type calcium channel in myocardial tissue might result in multiple cardiac disorders such as a prolonged QT interval. Therefore, QT prolongation is an independent risk factor of cardiovascular disease in patients with diabetes mellitus. Metformin, a hypoglycemic agent, is widely known to effectively reduce the occurrence of macrovascular diseases. The aim of the present study was to evaluate the effect of metformin on prolonged QT interval and to explore potential ionic mechanisms induced by diabetes. Diabetic mouse models were established with streptozotocin and an electrocardiogram was used to monitor the QT interval after 4 weeks of metformin treatment in each group. Action potential duration (APD) and L-type calcium current (I(Ca-L)) were detected by patch-clamp in isolated mice ventricular cardiomyocytes and neonatal cardiomyocytes of mice. The expression levels of CACNA1C mRNA and Cav1.2 were measured by real-time PCR, western blot and immunofluorescence. A shortened QT interval was observed after 4 weeks of metformin treatment in diabetic mice. Patch-clamp results revealed that both APD and I(Ca-L) were shortened in mouse cardiomyocytes. Furthermore, the expression levels of CACNA1C mRNA and Cav1.2 were decreased in the metformin group. The same results were also obtained in cultured neonatal mice cardiomyocytes. Overall, these results verify that metformin could shorten a prolonged QT interval by inhibiting the calcium current, suggesting that metformin may play a role in the electrophysiology underlying diabetic cardiopathy.
format Online
Article
Text
id pubmed-7300225
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-73002252020-06-26 Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach Wang, Hui Wang, Cao Lu, Yuan Yan, Yan Leng, Dongjing Tian, Shanshan Zheng, Dongjie Wang, Zhiguo Bai, Yunlong Front Pharmacol Pharmacology The incidence and mortality of cardiovascular disease in diabetic patients are 2-3 times higher than those in non-diabetic patients. Abnormal function of the L-type calcium channel in myocardial tissue might result in multiple cardiac disorders such as a prolonged QT interval. Therefore, QT prolongation is an independent risk factor of cardiovascular disease in patients with diabetes mellitus. Metformin, a hypoglycemic agent, is widely known to effectively reduce the occurrence of macrovascular diseases. The aim of the present study was to evaluate the effect of metformin on prolonged QT interval and to explore potential ionic mechanisms induced by diabetes. Diabetic mouse models were established with streptozotocin and an electrocardiogram was used to monitor the QT interval after 4 weeks of metformin treatment in each group. Action potential duration (APD) and L-type calcium current (I(Ca-L)) were detected by patch-clamp in isolated mice ventricular cardiomyocytes and neonatal cardiomyocytes of mice. The expression levels of CACNA1C mRNA and Cav1.2 were measured by real-time PCR, western blot and immunofluorescence. A shortened QT interval was observed after 4 weeks of metformin treatment in diabetic mice. Patch-clamp results revealed that both APD and I(Ca-L) were shortened in mouse cardiomyocytes. Furthermore, the expression levels of CACNA1C mRNA and Cav1.2 were decreased in the metformin group. The same results were also obtained in cultured neonatal mice cardiomyocytes. Overall, these results verify that metformin could shorten a prolonged QT interval by inhibiting the calcium current, suggesting that metformin may play a role in the electrophysiology underlying diabetic cardiopathy. Frontiers Media S.A. 2020-06-11 /pmc/articles/PMC7300225/ /pubmed/32595491 http://dx.doi.org/10.3389/fphar.2020.00614 Text en Copyright © 2020 Wang, Wang, Lu, Yan, Leng, Tian, Zheng, Wang and Bai http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Wang, Hui
Wang, Cao
Lu, Yuan
Yan, Yan
Leng, Dongjing
Tian, Shanshan
Zheng, Dongjie
Wang, Zhiguo
Bai, Yunlong
Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach
title Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach
title_full Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach
title_fullStr Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach
title_full_unstemmed Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach
title_short Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach
title_sort metformin shortens prolonged qt interval in diabetic mice by inhibiting l-type calcium current: a possible therapeutic approach
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300225/
https://www.ncbi.nlm.nih.gov/pubmed/32595491
http://dx.doi.org/10.3389/fphar.2020.00614
work_keys_str_mv AT wanghui metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT wangcao metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT luyuan metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT yanyan metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT lengdongjing metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT tianshanshan metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT zhengdongjie metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT wangzhiguo metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach
AT baiyunlong metforminshortensprolongedqtintervalindiabeticmicebyinhibitingltypecalciumcurrentapossibletherapeuticapproach