SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart
Abstract Background Hyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor has recently been reported to improve glycaemic control in patients with type 2 diabetes in an i...
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Format: | Article |
Language: | English |
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BMC
2019-02-01
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Series: | Cardiovascular Diabetology |
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Online Access: | http://link.springer.com/article/10.1186/s12933-019-0816-2 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chenguang Li Jie Zhang Mei Xue Xiaoyu Li Fei Han Xiangyang Liu Linxin Xu Yunhong Lu Ying Cheng Ting Li Xiaochen Yu Bei Sun Liming Chen |
spellingShingle |
Chenguang Li Jie Zhang Mei Xue Xiaoyu Li Fei Han Xiangyang Liu Linxin Xu Yunhong Lu Ying Cheng Ting Li Xiaochen Yu Bei Sun Liming Chen SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart Cardiovascular Diabetology Type 2 diabetes mellitus SGLT2 Empagliflozin Oxidative stress Myocardial fibrosis |
author_facet |
Chenguang Li Jie Zhang Mei Xue Xiaoyu Li Fei Han Xiangyang Liu Linxin Xu Yunhong Lu Ying Cheng Ting Li Xiaochen Yu Bei Sun Liming Chen |
author_sort |
Chenguang Li |
title |
SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart |
title_short |
SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart |
title_full |
SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart |
title_fullStr |
SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart |
title_full_unstemmed |
SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart |
title_sort |
sglt2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart |
publisher |
BMC |
series |
Cardiovascular Diabetology |
issn |
1475-2840 |
publishDate |
2019-02-01 |
description |
Abstract Background Hyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor has recently been reported to improve glycaemic control in patients with type 2 diabetes in an insulin-independent manner. The aim of this study was to investigate the effect of empagliflozin on myocardium injury and the potential mechanism in type 2 diabetic KK-Ay mice. Methods Thirty diabetic KK-Ay mice were administered empagliflozin (10 mg/kg/day) by oral gavage daily for 8 weeks. After 8 weeks, heart structure and function were evaluated by echocardiography. Oxidants and antioxidants were measured and cardiac fibrosis was analysed using immunohistochemistry, Masson’s trichrome stain and Western blot. Results Results showed that empagliflozin improved diabetic myocardial structure and function, decreased myocardial oxidative stress and ameliorated myocardial fibrosis. Further study indicated that empagliflozin suppressed oxidative stress and fibrosis through inhibition of the transforming growth factor β/Smad pathway and activation of Nrf2/ARE signaling. Conclusions Glycaemic control with empagliflozin significantly ameliorated myocardial oxidative stress injury and cardiac fibrosis in diabetic mice. Taken together, these results indicate that the empagliflozin is a promising agent for the prevention and treatment of diabetic cardiomyopathy. |
topic |
Type 2 diabetes mellitus SGLT2 Empagliflozin Oxidative stress Myocardial fibrosis |
url |
http://link.springer.com/article/10.1186/s12933-019-0816-2 |
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doaj-4ba6523e673b443a95b9427ec8314d142020-11-25T01:43:44ZengBMCCardiovascular Diabetology1475-28402019-02-0118111310.1186/s12933-019-0816-2SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heartChenguang Li0Jie Zhang1Mei Xue2Xiaoyu Li3Fei Han4Xiangyang Liu5Linxin Xu6Yunhong Lu7Ying Cheng8Ting Li9Xiaochen Yu10Bei Sun11Liming Chen12NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyNHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Metabolic Diseases Hospital & Tianjin Institute of EndocrinologyAbstract Background Hyperglycaemia associated with myocardial oxidative stress and fibrosis is the main cause of diabetic cardiomyopathy. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor has recently been reported to improve glycaemic control in patients with type 2 diabetes in an insulin-independent manner. The aim of this study was to investigate the effect of empagliflozin on myocardium injury and the potential mechanism in type 2 diabetic KK-Ay mice. Methods Thirty diabetic KK-Ay mice were administered empagliflozin (10 mg/kg/day) by oral gavage daily for 8 weeks. After 8 weeks, heart structure and function were evaluated by echocardiography. Oxidants and antioxidants were measured and cardiac fibrosis was analysed using immunohistochemistry, Masson’s trichrome stain and Western blot. Results Results showed that empagliflozin improved diabetic myocardial structure and function, decreased myocardial oxidative stress and ameliorated myocardial fibrosis. Further study indicated that empagliflozin suppressed oxidative stress and fibrosis through inhibition of the transforming growth factor β/Smad pathway and activation of Nrf2/ARE signaling. Conclusions Glycaemic control with empagliflozin significantly ameliorated myocardial oxidative stress injury and cardiac fibrosis in diabetic mice. Taken together, these results indicate that the empagliflozin is a promising agent for the prevention and treatment of diabetic cardiomyopathy.http://link.springer.com/article/10.1186/s12933-019-0816-2Type 2 diabetes mellitusSGLT2EmpagliflozinOxidative stressMyocardial fibrosis |