The DOI matches its Crossref record; 60 of the 63 references it cites were found in a registry or an index.
Empagliflozin rescues diabetic myocardial microvascular injury via AMPK-mediated inhibition of mitochondrial fission
Open accessAbstract
Impaired cardiac microvascular function contributes to diabetic cardiovascular complications although effective therapy remains elusive. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor recently approved for treatment of type 2 diabetes, promotes glycosuria excretion and offers cardioprotective actions beyond its glucose-lowering effects. This study was designed to evaluate the effect of empagliflozin on cardiac microvascular injury in diabetes and the underlying mechanism involved with a focus on mitochondria. Our data revealed that empagliflozin improved diabetic myocardial structure and function, preserved cardiac microvascular barrier function and integrity, sustained eNOS phosphorylation and endothelium-dependent relaxation, as well as improved microvessel density and perfusion. Further study suggested that empagliflozin exerted its effects through inhibition of mitochondrial fission in an adenosine monophosphate (AMP)-activated protein kinase (AMPK)-dependent manner. Empagliflozin restored AMP-to-ATP ratio to trigger AMPK activation, suppressed Drp1 S616 phosphorylation, and increased Drp1 S637 phosphorylation, ultimately leading to inhibition of mitochondrial fission. The empagliflozin-induced inhibition of mitochondrial fission preserved cardiac microvascular endothelial cell (CMEC) barrier function through suppressed mitochondrial reactive oxygen species (mtROS) production and subsequently oxidative stress to impede CMEC senescence. Empagliflozin-induced fission loss also favored angiogenesis by promoting CMEC migration through amelioration of F-actin depolymerization. Taken together, these results indicated the therapeutic promises of empagliflozin in the treatment of pathological microvascular changes in diabetes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Empagliflozin exerted its protective roles via inhibition of AMPK-dependent mitochondrial fission [229].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [229]
In the citing paper
“Empagliflozin recovered the AMP-to-ATP ratio that is necessary for triggering AMPK activation [229].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [229]
In the citing paper
“In the meantime, DRP1-S616 phosphorylation was decreased, while DRP1-S637 phosphorylation was increased, ultimately leading to mitochondrial fission [229].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [229]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
1 retracted
Zhou, H., Du, W., Li, Y., Chen, S., Hu, N., Ma, S., Wang, W., & Ren, J. T. (2017) · Journal of Pineal Research · doi:10.1111/jpi.12450 · Cited by 292
RetractedEmpagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., Mattheus, M., Devins, T., Johansen, O. E., Woerle, H. J., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1504720 · Cited by 12,315
AMP-activated protein kinase mediates mitochondrial fission in response to energy stress
Toyama, E. Q., Herzig, S., Courchet, J., Lewis, T. L., Losón, O. C., Hellberg, K., Young, N. P., Chen, H., Polleux, F., Chan, D. C., et al. (2016) · Science · doi:10.1126/science.aab4138 · Cited by 1,085
Mitochondrial Fission Inhibitors Suppress Endothelin-1-Induced Artery Constriction
Chen, C., Gao, J., Liu, M., Li, S., Xuan, X., Zhang, X., Zhang, X.-Y., Wei, Y., Zhen, C., Jin, J., et al. (2017) · Cellular Physiology and Biochemistry · doi:10.1159/000479536 · Cited by 782
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
(2016) · New England Journal of Medicine · doi:10.1056/nejmc1600827 · Cited by 700
Mitochondrial composition and function under the control of hypoxia
Fuhrmann, D. C., & Brüne, B. (2017) · Redox Biology · doi:10.1016/j.redox.2017.02.012 · Cited by 665 · cited 1×
“The mitochondrial content is modest in endothelial cells compared to other cell types with a higher energy requirement, indicating a primary role for mitochondria as essential signaling organelles in vascular endothelium [10,11].”
BackgroundMitochondrial dynamics in type 2 diabetes: Pathophysiological implications
Rovira-Llopis, S., Bañuls, C., Diaz-Morales, N., Hernandez-Mijares, A., Rocha, M., & Victor, V. M. (2017) · Redox Biology · doi:10.1016/j.redox.2017.01.013 · Cited by 657 · cited 2×
“Besides, hyperglycemia-triggered mitochondrial fission may be lessened by mitophagy, a repair system for the mitochondrial homeostasis via timely clearance of the mitochondrial debris [15,53].”
BackgroundEndothelial Cell Metabolism in Normal and Diseased Vasculature
Eelen, G., de Zeeuw, P., Simons, M., & Carmeliet, P. (2015) · Circulation Research · doi:10.1161/circresaha.116.302855 · Cited by 637 · cited 1×
“Therefore, the hunt for means to protect the cardiac microvasculature against hyperglycemic damage is essential to retard or alleviate diabetic macrovascular complications [4].”
BackgroundChilton, R., Tikkanen, I., Cannon, C. P., Crowe, S., Woerle, H. J., Broedl, U. C., & Johansen, O. E. (2015) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12572 · Cited by 507 · cited 1×
“Considerable evidence has documented the ability of empagliflozin to reduce SBP through facilitating osmotic diuresis [38].”
BackgroundWang, W., Wang, Y., Long, J., Wang, J., Haudek, S. B., Overbeek, P., Chang, B. H. J., Schumacker, P. T., & Danesh, F. R. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.009 · Cited by 476 · cited 3×
“ROCK triggers fission by phosphorylating Drp1 at the Serine(616) (Ser(616)) residue in kidney podocytes and endothelial cells [12].”
Background
Flagged first, then by citations
3 of the 63 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Items 501–547 of 547
Zhou, J., Shi, M., Li, M., Cheng, L., Yang, J., & Huang, X. (2021) · Cell Stress and Chaperones · doi:10.1007/s12192-021-01227-z
RetractedPiekarowicz, A. (1979) · PubMed
Колесникова, А. А., Колесников, О. Л., & Тарабрина, Ю. О. (2021) · Естественные и Технические Науки · doi:10.37882/2223-2966.2021.09.16
Vowel Shift in Northern New Mexico Chicano English
Ho, J. (1993) · Mester
Progress in Drug Therapy of Coronary Microvascular Endothelial Dysfunction
张, 梦. (2022) · Advances in Clinical Medicine · doi:10.12677/acm.2022.1291171
A metabolically healthy lifestyle
Andriessen, C. (2023) · Research Publications (Maastricht University) · doi:10.26481/dis.20230706ca
SGLT2 inhibitors: a new weapon against aging?
Frigé, C. (2023) · The Journal of AMD · doi:10.36171/jamd23.26.3.2
AL-Shimaysawee, O. S., Rizij, F. A., & Wasfi, R. M. A. H. (2024) · Journal of Contemporary Medical Sciences · doi:10.22317/jcms.v10i1.1483
Mitochondrial Dynamics and Research Status of Hypoglycemic Drugs and Type 2 Diabetes Mellitus
屈, 颖. (2024) · Journal of Clinical Personalized Medicine · doi:10.12677/jcpm.2024.32033
Alotaibi, F. M., Almazam, . A., Alotaibi, ., Emam, . M., Alqahtani, . S., Alheggi, . I., Alanazi, . F., Alharbi, . K., Alhamed, . A., Ali, . I. A., et al. (2021) · International Journal of Health Sciences · doi:10.53730/ijhs.v5ns1.15088
SGLT2 Inhibitors and Mechanism of Cardiovascular Benefits in Type 2 Diabetes
Nandave, M. (2024) · Springer eBooks · doi:10.1007/978-981-97-7568-2_2
Nandave, M. (2024) · Springer eBooks · doi:10.1007/978-981-97-7568-2_3
Antiglycation Efficacy: Unknown Pleiotropicity of Known Drugs
Зайцева, Е. Н., Lebedev, P. A., Юрьевна, С. Т., Масленникова, Н. О., & Шарова, О. В. (2024) · Pharmaceutical Chemistry Journal · doi:10.1007/s11094-024-03259-y
Lee, J.-E., Kim, B. G., & Won, J. C. (2025) · Journal of Lipid and Atherosclerosis · doi:10.12997/jla.2025.14.1.46
Li, D., Xinyve, Z., Wang, Q., & Yanwei, D. (2025) · Journal of Cardiology and Cardiovascular Medicine · doi:10.29328/journal.jccm.1001209
Guo, J., Wang, S., Wan, X., Liu, X., Wang, Z., Liang, C., Zhang, Z., Wang, Y., Yan, M., Wu, P., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25026025
Chen, Y., Li, S., Guan, B., Yan, X., Huang, C., Du, Y., Yang, F., Zhang, N., Li, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26718411
Guo, J., Wang, S., Wan, X., Liu, X., Wang, Z., Liang, C., Zhang, Z., Wang, Y., Yan, M., Wu, P., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25025833
Chen, Y., Li, S., Guan, B., Yan, X., Huang, C., Du, Y., Yang, F., Zhang, N., Li, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26718405
Chen, Y., Li, S., Guan, B., Yan, X., Huang, C., Du, Y., Yang, F., Zhang, N., Li, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26718417
Yang, W., Li, X., He, L., Zhu, S., Lai, S., Zhang, X., Huang, Z., Yu, B., Cui, C., & Wang, Q. (2024) · Figshare · doi:10.6084/m9.figshare.26590278
Ouyang, L., Qiu, D., Fu, X., Wu, A., Yang, P., Yang, Z., Wang, Q., Yan, L., & Xiao, R. (2022) · Figshare · doi:10.6084/m9.figshare.20430696
Liu, M., Wei, X., Zheng, Z., Xie, E., Yu, Q., Gao, Y., Ma, J., & Yang, L. (2024) · Figshare · doi:10.6084/m9.figshare.25853021
Chen, Y., Li, S., Guan, B., Yan, X., Huang, C., Du, Y., Yang, F., Zhang, N., Li, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26718396
Chen, Y., Li, S., Guan, B., Yan, X., Huang, C., Du, Y., Yang, F., Zhang, N., Li, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26718399
Shi, X., Liu, C., Chen, J., Zhou, S., Li, Y., Zhao, X., Xing, J., Xue, J., Liu, F., & Li, F. (2024) · Figshare · doi:10.6084/m9.figshare.26611088
Chen, Y., Li, S., Guan, B., Yan, X., Huang, C., Du, Y., Yang, F., Zhang, N., Li, Y., Lu, J., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26718390
Huang, X., Xiaoxiang, W. A. N. G., JIANG, Y., Shen, K., Zhenlei, J. I. A., Xiangdong, M. A., Zhong, B., He, Y., & Lou, M. (2025) · Journal of Zhejiang University (Medical Sciences) · doi:10.3724/zdxbyxb-2025-0474
Sodium-glucose cotransporter-2 inhibitors and sepsis: a story with two tails or with one tail?
Afşar, B., Afşar, R. E., Tuttle, K. R., & Lentine, K. L. (2026) · Inflammopharmacology · doi:10.1007/s10787-025-02091-4
“SGLT2i may play a protective role in these processes by improving AMPK signaling (Hawley et al. 2016; Zhou et al. 2018 ).”
Chen, L., Wang, Q., Shen, M., Li, M., Zhu, Y., Zheng, C., Ma, S., Lin, H., Fu, X., Zhang, R., et al. (2026) · Interdisciplinary medicine · doi:10.1002/inmd.70090
Zaini, L. M., Syukri, M., Kartasasmita, A., Gondhowiardjo, T. D., & Lesmana, R. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1013249
Li, B., Shi, Y., Yang, K., Liu, C., Miao, Q., Yibulayin, K., Lei, Z., Li, B., Gong, S., Yu, Q., et al. (2026) · Clinical Science · doi:10.1042/cs20256842
Sodium glucose transporter 2 inhibitors for heart failure
Usuda, D., Furukawa, D., Imaizumi, R., Ono, R., Kaneoka, Y., Nakajima, E., Kato, M., Sugawara, Y., Shimizu, R., Inami, T., et al. (2026) · World Journal of Cardiology · doi:10.4330/wjc.v18.i3.118227
Protective effect of SGLT2 inhibitors on cardiovascular remodeling
Matsushita, K. (2022) · theses.fr (ABES) · doi:10.70675/a461e811zf66fz4443za0efz481618885013
Yang, Y., Zhou, W., Yang, M., Tang, S. C. W., & Liu, B.-C. (2026) · Frontiers in Pharmacology · doi:10.3389/fphar.2026.1800868
“Empagliflozin also improved cardiac microvascular perfusion through lessened vascular remodeling and endothelial function via improving eNOS phosphorylation and activation of AMPK pathway in diabetic mice and hyperglycemia-mediated cardiac microvascular endothelial cell (Zhou et al., 2018).”
El‐Kashef, D. H., Shawky, N. O., Mahdi, L., Sewilam, H. M., & Saleh, M. A. (2026) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-026-05214-y
“Empa has been shown to have anti-inflammatory effects through SGLT-2-independent pathways, such as reduction of superoxide generation, and repression of oxidative stress (Zhou et al. 2018).”
Chang, X., Zhang, Y., Xu, W., Guo, Z., Ong, S., Liu, N., Li, Y., Zhou, H., Bai, Y., & Meng, M. (2026) · Phytomedicine · doi:10.1016/j.phymed.2026.158208
Zhang, Y., Zhao, Y., Luo, Y., Wang, L., Liao, J., Lu, H., Zhang, X., & Ji, X. (2026) · Inflammation · doi:10.1007/s10753-026-02507-5 · Cited by 1
Cheng, S.-A., & Lim, J. H. (2026) · Life · doi:10.3390/life16071135
“…of the AMPK pathway by empagliflozin suppresses the phosphorylation https://doi.org/10.3390/life16071135 of Drp1, which ultimately inhibits mitochondrial fission, leading to reduced oxidative stress, preserved ATP production, and improved mitochondrial integrity and endothelial function [37].”
InfluentialŠantić, R., Martinovic, L., Kumrić, M., Pavlović, N., Martinović, D., Jukić, L., Pogorelić, Z., & Božić, J. (2026) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd13070321 · Cited by 1
“In coronary microvascular endothelial cells, this promotes DRP1-dependent fission, impairs FUNDC1-and PINK1/Parkin-mediated mitophagy, suppresses PGC-1 α -dependent biogenesis, and increases endothelial apoptosis [30,34–36, 56, 57 ].”
InfluentialBreaking barriers in pulmonary health of patients with metabolic diseases: senolytics and beyond
Rennerova, M., Žaloudíková, M., Haluzík, M., & Hubáčková, S. (2026) · Frontiers in Aging · doi:10.3389/fragi.2026.1812724
“Empagliflozin enhances mitochondrial function and supports autophagy, aiding the clearance of damaged and senescent cells (Mattii et al., 2024; Zhou et al., 2018).”
Irisin upregulation as a contributory mechanism for the therapeutic benefits of SGLT-2 inhibitors
Noto, N. M., Martin, K., Fidelia, S., Parmar, M. S., Cubeddu, L. X., Gurusamy, N., & Speth, R. C. (2026) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2026.109090
Zhang, Y., Li, Y., Huang, J., Chen, X., Luan, J., Noor, R., Hussain, J., He, J., & 邵龙泉 (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.115237
Recent advances in mitochondrial fission and fusion in diabetic cardiomyopathy
Hao, J., Zhang, X., Tian, X., & Su, J. (2026) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2026.1897303
“…fragmentation reduces nitric oxide bioavailability, disrupts barrier function, and increases susceptibility to ferroptosis; empagliflozin and USP33-dependent stabilization of ATG7 protect the diabetic microvasculature by restraining DRP1/ FIS1-mediated remodeling and restoring autophagy (14, 31).”
InfluentialThe therapeutic potential of melatonin: Focus on the SIRT1 signaling pathway
Vahidinia, Z., Behdarvandy, M., Tameh, A. A., Barati, S., & Yasamian, A. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12815-6
“There is evidence indicating that endothelial dysfunction is involved in the development of cardiovascular complications related to DM. DM and elevated blood glucose levels can lead to structural and functional changes in endothelial cells, which contribute to dysfunction in CMECs [21, 22].”
Bartoszewicz, M., & Niemczyk, M. (2026) · Aging · doi:10.18632/aging.206426
Yan, M., 程玲莉, Chen, C., Yang, D., Liu, H., Ding, G., & Jian, Y. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.104070
Metadata
- Authors
- Zhou, H., Wang, S., Zhu, P., Hu, S., Chen, Y., & Ren, J.
- Affiliations
- Chinese PLA General Hospital (CN)
- University of Wyoming (US)
- Corresponding author
- Zhou, Hao
- Chen, Yundai
- Ren, Jun
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 15
- Pages
- 335-346
- ISSN
- 2213-2317 (ISSN-L)
- PMC
- PMC5756062
- OpenAlex
- W2777514005
- Cited by
- 550
- References
- 63
- Citations by year
- 2026: 34 · 2025: 53 · 2024: 87 · 2023: 71 · 2022: 71 · 2021: 65 · 2020: 63 · 2019: 53 · 2018: 50
- FWCI
- 35.91
- Type
- journal article
- Language
- en
- Update notices
- erratum (2024-05-01)
- Open access
- gold
- doi.org
- Licence
- Locations
- Redox Biology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81441008, 81030002, 81102079, 81270186)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- empagliflozin, SGLT2 inhibitors, diabetic cardiomyopathy, mitochondrial fission, AMPK, Drp1 phosphorylation, endothelial barrier function, endothelial cell senescence, mitochondrial reactive oxygen species, oxidative stress, angiogenesis, endothelial cell migration, F-actin depolymerization, eNOS phosphorylation, type 2 diabetes
- MeSH terms
- AMP-Activated Protein Kinase Kinases, Animals, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Glucosides, Heart Injuries, Humans, Mitochondria, Protein Kinases, Endothelial Cells, Mice, Mitochondrial Dynamics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
