Vildagliptin improves high glucose-induced endothelial mitochondrial dysfunction via inhibiting mitochondrial fission
Open accessAbstract
The dipeptidyl peptidase 4 inhibitor vildagliptin (VLD), a widely used anti-diabetic drug, exerts favourable effects on vascular endothelium in diabetes. We determined for the first time the improving effects of VLD on mitochondrial dysfunction in diabetic mice and human umbilical vein endothelial cells (HUVECs) cultured under hyperglycaemic conditions, and further explored the mechanism behind the anti-diabetic activity. Mitochondrial ROS (mtROS) production was detected by fluorescent microscope and flow cytometry. Mitochondrial DNA damage and ATP synthesis were analysed by real time PCR and ATPlite assay, respectively. Mitochondrial network stained with MitoTracker Red to identify mitochondrial fragmentation was visualized under confocal microscopy. The expression levels of dynamin-related proteins (Drp1 and Fis1) were determined by immunoblotting. We found that VLD significantly reduced mtROS production and mitochondrial DNA damage, but enhanced ATP synthesis in endothelium under diabetic conditions. Moreover, VLD reduced the expression of Drp1 and Fis1, blocked Drp1 translocation into mitochondria, and blunted mitochondrial fragmentation induced by hyperglycaemia. As a result, mitochondrial dysfunction was alleviated and mitochondrial morphology was restored by VLD. Additionally, VLD promoted the phosphorylation of AMPK and its target acetyl-CoA carboxylase in the setting of high glucose, and AMPK activation led to a decreased expression and activation of Drp1. In conclusion, VLD improves endothelial mitochondrial dysfunction in diabetes, possibly through inhibiting Drp1-mediated mitochondrial fission in an AMPK-dependent manner.
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Vildagliptin improved mitochondrial dysfunction in diabetic endothelial cells, possibly by blunting DRP1-dependent mitochondrial fission by inducing AMPK activation.
“Vildagliptin improved mitochondrial dysfunction in diabetic ECs, possibly by blunting DRP1-dependent mitochondrial fission by inducing AMPK activation [230].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [230]
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AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
- Authors
- Liu, H., Xiang, H., Zhao, S., Sang, H., Lv, F., Chen, R., Shu, Z., Chen, A. F., Chen, S., & Lu, H.
- Affiliations
- First Affiliated Hospital of Zhengzhou University (CN)
- Third Xiangya Hospital (CN)
- First Affiliated Hospital of Xinxiang Medical University (CN)
- University of Pittsburgh (US)
- Central South University (CN)
- Corresponding author
- Chen, Shuhua
- Lu, Hongwei
- ORCID
- Venue
- Journal of Cellular and Molecular Medicine
- Publisher
- Wiley
- Published
- 2018-11-16
- Volume
- 23
- Issue
- 2
- Pages
- 798-810
- ISSN
- 1582-1838 (ISSN-L)
- 1582-4934
- PMC
- PMC6349192
- OpenAlex
- W2901021262
- Cited by
- 52
- References
- 43
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 3 · 2023: 10 · 2022: 11 · 2021: 7 · 2020: 10 · 2019: 3 · 2017: 1
- FWCI
- 1.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Cellular and Molecular Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81470593)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- vildagliptin, DPP-4 inhibitors, mitochondrial fission, mitochondrial fragmentation, hyperglycemia, diabetes mellitus, mitochondrial reactive oxygen species, mitochondrial DNA damage, ATP production, Drp1, Fis1, AMPK, acetyl-CoA carboxylase, vascular endothelium
- MeSH terms
- Vildagliptin, Acetyl-CoA Carboxylase, Animals, Diabetes Mellitus, Experimental, DNA, Mitochondrial, Endothelium, Vascular, Gene Expression Regulation, Glucose, Humans, Hypoglycemic Agents, Male, Mice, Inbred C57BL, Mice, Transgenic, Mitochondria, Phosphorylation, Signal Transduction, Reactive Oxygen Species, Mitochondrial Proteins, Dynamins, Mice, AMP-Activated Protein Kinases, Human Umbilical Vein Endothelial Cells, Mitochondrial Dynamics
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