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

Yifeng Gao1, En Li1, Fang Li1

  • 1The Second Affiliated Hospital, Zhengzhou University, Zhengzhou, 450014, People's Republic of China.

Cellular and Molecular Life Sciences : CMLS
|June 25, 2025
PubMed
Abstract

Insights

Dapagliflozin effectively protects against myocardial mitochondrial injury in type 2 diabetes by improving mitochondrial function and reducing fibrosis. This suggests sortilin (SORT1) as a potential therapeutic target for diabetic heart conditions.

Area of Science:

  • Cardiovascular Research
  • Metabolic Disorders
  • Mitochondrial Biology

Background:

  • Type 2 diabetes (T2D) poses significant risks for myocardial injury, particularly mitochondrial damage.
  • Diabetic cardiomyopathy is a major complication, necessitating effective therapeutic strategies.

Purpose of the Study:

  • To investigate the therapeutic effects of dapagliflozin on myocardial mitochondrial injury in diabetic conditions.
  • To elucidate the underlying mechanisms, including the role of sortilin (SORT1), in dapagliflozin's protective actions.

Main Methods:

  • Utilized high-glucose, high-fat cell models and a type 2 diabetic mouse model (STZ-induced).
  • Administered dapagliflozin and employed siRNA to silence SORT1.
  • Conducted analyses including qPCR, Western blot, ROS assays, electron microscopy, and Masson's staining.

Main Results:

  • Diabetic conditions induced mitochondrial damage, characterized by reduced respiratory chain function, increased ROS, and structural abnormalities.
  • Silencing SORT1 mimicked diabetic mitochondrial dysfunction, indicating its crucial role.
  • Dapagliflozin treatment significantly ameliorated mitochondrial dysfunction and myocardial fibrosis in both in vitro and in vivo models.

Conclusions:

  • Dapagliflozin demonstrates therapeutic potential in mitigating diabetic myocardial mitochondrial injury.
  • Identified a novel mechanism involving SORT1, suggesting it as a potential therapeutic target for diabetic heart disease.
Keywords:
DapagliflozinDiabetesMitochondriaMyocardiumSortilin

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