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Cited by 263Mitochondrial Function and PathologyCell death mechanisms and regulationMetabolism, Diabetes, and Cancer

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Metformin Prevents High-Glucose–Induced Endothelial Cell Death Through a Mitochondrial Permeability Transition-Dependent Process

Detaille, Dominique, Guigas, Bruno, Chauvin, Christiane, Batandier, Cécile, Fontaine, Eric, Wiernsperger, Nicolas, Leverve, Xavier·2005·Diabetes
DOI 10.2337/diabetes.54.7.2179
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Abstract

Hyperglycemia-induced oxidative stress is detrimental for endothelial cells, contributing to the vascular complications of diabetes. The mitochondrial permeability transition pore (PTP) is an oxidative stress–sensitive channel involved in cell death; therefore, we have examined its potential role in endothelial cells exposed to oxidative stress or high glucose level. Metformin, an antihyperglycemic agent used in type 2 diabetes, was also investigated because it inhibits PTP opening in transformed cell lines. Cyclosporin A (CsA), the reference PTP inhibitor, and a therapeutic dose of metformin (100 μmol/l) led to PTP inhibition in permeabilized human microvascular endothelial cells (HMEC-1). Furthermore, exposure of intact HMEC-1 or primary endothelial cells from either human umbilical vein or bovine aorta to the oxidizing agent tert-butylhydroperoxide or to 30 mmol/l glucose triggered PTP opening, cytochrome c decompartmentalization, and cell death. CsA or metformin prevented all of these effects. The antioxidant N-acetyl-l-cysteine also prevented hyperglycemia-induced apoptosis. We conclude that 1) elevated glucose concentration leads to an oxidative stress that favors PTP opening and subsequent cell death in several endothelial cell types and 2) metformin prevents this PTP opening–related cell death. We propose that metformin improves diabetes-associated vascular disease both by lowering blood glucose and by its effect on PTP regulation.

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Crossref · 10.2337/diabetes.54.7.2179

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Metadata

Authors
Detaille, D., Guigas, B., Chauvin, C., Batandier, C., Fontaine, E., Wiernsperger, N., & Leverve, X.
Affiliations
  • Laboratoire de Bioénergétique Fondamentale et Appliquée, Institut National de la Santé et de la Recherche Médicale EMI-0221, Université Joseph Fourier, Grenoble, France
  • Inserm (FR)
  • Merck Serono S.A.S. (France) (FR)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2005-07-01
Volume
54
Issue
7
Pages
2179-2187
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.54.7.2179
OpenAlex
W2163301537
Cited by
263
References
40
Citations by year
2026: 4 · 2025: 8 · 2024: 10 · 2023: 7 · 2022: 14 · 2021: 13 · 2020: 19 · 2019: 19 · 2018: 12 · 2017: 7 · 2016: 16 · 2015: 17 · 2014: 12 · 2013: 12 · 2012: 15
FWCI
5.02
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
metformin, mitochondrial permeability transition pore, endothelial cell death, hyperglycemia, oxidative stress, cyclosporine, cytochrome c release, apoptosis, tert-butyl hydroperoxide, N-acetylcysteine, diabetic vascular complications, type 2 diabetes, microvascular endothelial cells
MeSH terms
Cell Line, Endothelium, Vascular, Glucose, Humans, Metformin, Microcirculation, Mitochondria, Permeability, Skin, Cell Death

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