Evidence mapPaperPMID 40560392Full record

ArticleCellular and molecular life sciences : CMLS2025

Dapagliflozin alleviates mitochondrial damage in the myocardium under diabetic conditions by targeting sortilin.

Yifeng Gao, En Li, Fang Li, Ying Cui, Qi Shu, Yan Zhang, Lijuan Kong, Han Li, Xiaoyu Yang

Abstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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2citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Yifeng Gao *The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, 450014, People's Republic of China.
En Li *The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, 450014, People's Republic of China.
Fang Li *The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, 450014, People's Republic of China.
Ying CuiPathology Teaching and Research Office, Zhengzhou Health Vocational College, Zhengzhou, 450001, People's Republic of China.
Qi ShuSchool of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.
Yan ZhangCenter for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Lijuan KongThe Second Affiliated Hospital, Zhengzhou University, Zhengzhou, 450014, People's Republic of China.
Han LiThe Second Affiliated Hospital, Zhengzhou University, Zhengzhou, 450014, People's Republic of China.
Xiaoyu YangThe Second Affiliated Hospital, Zhengzhou University, Zhengzhou, 450014, People's Republic of China. yangxy1900@zzu.edu.cn.ORCID http://orcid.org/0000-0001-8858-8619

Funding

The Second Affiliated Hospital, Zhengzhou University. 202004047
6 · The paper itself

Abstract

backgroundType 2 diabetes patients are particularly vulnerable to myocardial injury, including mitochondrial damage in the myocardium. This study aims to evaluate the therapeutic potential and mechanisms of dapagliflozin in mitigating myocardial mitochondrial injury under diabetic conditions.

methodsA cell model was established using a high-glucose, high-fat combination. Dapagliflozin was dissolved in Dimethyl sulfoxide (DMSO) and added to the culture medium. A type 2 diabetic mouse model was induced by high-fat feeding combined with Streptozotocin (STZ) injection, with dapagliflozin administered via oral gavage. SORT1 was silenced using siRNA. Phenotypic evaluation and mechanistic analysis were performed through qPCR, Western blot (WB), activity assays, Reactive Oxygen Species (ROS) measurement, transmission electron microscopy, and Masson's staining.

resultsIn vitro studies, we demonstrated that under diabetic conditions, mitochondrial damage was evident, characterized by a decrease in mitochondrial respiratory chain complex content, reduced complex activity, increased ROS levels, and structural damage to mitochondria. Silencing SORT1 resulted in a similar mitochondrial phenotype under diabetic conditions, highlighting the critical role of sortilin in mitochondrial function. Addition of dapagliflozin to the culture medium significantly improved mitochondrial dysfunction caused by high glucose and high fat, a finding also confirmed in the mouse model. Moreover, dapagliflozin alleviated myocardial fibrosis induced by diabetes in the mouse model.

conclusionsOur findings uncover a novel molecular mechanism through which dapagliflozin improves myocardial mitochondrial injury under diabetic conditions, suggesting SORT1 as a potential therapeutic target for treating myocardial injury in diabetes.

Indexed as

Adaptor Proteins, Vesicular TransportBenzhydryl CompoundsDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2GlucosidesMitochondriaMitochondria, HeartMyocardiumAnimalsMaleMiceMice, Inbred C57BLMyocytes, CardiacReactive Oxygen SpeciesSortilinAdaptor Proteins, Vesicular TransportBenzhydryl CompoundsdapagliflozinGlucosidesReactive Oxygen SpeciesSortilinDapagliflozinDiabetesMitochondriaMyocardiumSortilin

Identifiers

PMID40560392
PMCPMC12198091

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.