Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2023; 14(12): 1862-1876
Published online Dec 15, 2023. doi: 10.4239/wjd.v14.i12.1862
Empagliflozin ameliorates diabetic cardiomyopathy probably via activating AMPK/PGC-1α and inhibiting the RhoA/ROCK pathway
Na Li, Qiu-Xiao Zhu, Gui-Zhi Li, Ting Wang, Hong Zhou
Na Li, Qiu-Xiao Zhu, Gui-Zhi Li, Ting Wang, Hong Zhou, Department of Endocrinology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Author contributions: Li N, Zhu QX, Li GZ, Wang T, and Zhou H designed and coordinated the study; Li N, Zhu QX, Li GZ, and Zhou H performed the experiments, and acquired and analyzed the data; Li N interpreted the data; Li N and Zhou H wrote the manuscript; all authors approved the final version of the article.
Supported by Health Commission of Hebei Province, No. 20210196; S & T Program of Hebei, No. 22377726D.
Institutional review board statement: The study was reviewed and approved by the research ethics committee of the Second Hospital of Hebei Medical University Institutional Review Board (Approval No. 2022-AE136).
Conflict-of-interest statement: The authors declare no competing interests for this article.
Data sharing statement: The data of this study are available from the corresponding authors upon request.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hong Zhou, PhD, Chief Physician, Doctor, Department of Endocrinology, The Second Hospital of Hebei Medical University, No. 215, Heping West Road, Shijiazhuang 050000, Hebei Province, China. zhoubs2013@163.com
Received: September 21, 2023
Peer-review started: September 21, 2023
First decision: October 10, 2023
Revised: October 20, 2023
Accepted: November 17, 2023
Article in press: November 17, 2023
Published online: December 15, 2023
Processing time: 83 Days and 20.1 Hours
Core Tip

Core Tip: We established a diabetic cardiomyopathy model in db/db mice and treated the mice with empagliflozin for 8 wk, and found that empagliflozin observably improved cardiac function in diabetic mice, which was maybe related to activation of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and inhibition of the RhoA/ROCK pathway. In order to exclude the effects of metabolic improvement on the heart in vivo, in vitro experiment in high glucose conditions was performed. The results confirmed that the anti-oxidative stress and anti-apoptotic effects of empagliflozin on cardiomyocytes were achieved by activating AMPK/PGC-1α and inhibiting ROCK. Furthermore, the effects were independent of sodium-glucose cotransporter (SGLT)2 inhibition as no SGLT2 expression was detected on cardiomyocytes.