Dynamin-related protein 1 mediates high glucose induced pancreatic beta cell apoptosis
Open accessAbstract
The pancreatic beta cell dysfunction is critical cycle in the pathogenesis of diabetes. Hyperglycemia is one of factors that induce pancreatic beta cell dysfunction, but the underlying mechanisms have not been well elucidated. In this study, we reported that a mitochondrial fission modulator, Dynamin-related protein 1 (Drp-1), plays an important role in high glucose induced beta cell apoptosis. Drp-1 expressed in islet beta cells was increased drastically under hyperglycemia conditions. Induction of Drp-1 expression significantly promoted high glucose induced apoptosis in Drp-1WT (Drp-1 wild type) inducible beta cell line, but not in Drp-1K38A (a dominant negative mutant of Drp1) inducible beta cell line. We further demonstrated that mitochondrial fission, cytochrome C release, mitochondrial membrane potential decreased, caspase-3 activation and generation of reactive oxygen species were enhanced by induction of Drp-1WT, but prevented by Drp-1K38A in pancreatic beta cells under high glucose condition. These results indicated that Drp-1 mediates high glucose induced pancreatic beta cell apoptosis.
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Exposure to high levels of glucose and PA induced pancreatic β-cell mitochondrial fragmentation.
“Finally, exposure to high levels of glucose and PA induced pancreatic β-cell mitochondrial fragmentation, and preserving mitochondrial dynamics protected β cells from apoptosis (28, 29).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [28]
Preserving mitochondrial dynamics protected β cells from apoptosis.
“Finally, exposure to high levels of glucose and PA induced pancreatic β-cell mitochondrial fragmentation, and preserving mitochondrial dynamics protected β cells from apoptosis (28, 29).”
From Mitochondrial Fission Contributes to Mitochondrial Dysfunction and Insulin Resistance in Skeletal Muscle (2012) · cites this paper as [28]
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- Authors
- Men, X., Wang, H., Li, M., Cai, H., Xu, S., Zhang, W., Xu, Y., Ye, L., Yang, W., Wollheim, C. B., & Lou, J.
- Affiliations
- China-Japan Friendship Hospital (CN)
- University of Geneva (CH)
- Sun Yat-sen University (CN)
- Corresponding author
- Lou, Jinning
- ORCID
- Venue
- The International Journal of Biochemistry & Cell Biology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 41
- Issue
- 4
- Pages
- 879-890
- ISSN
- 1357-2725 (ISSN-L)
- OpenAlex
- W2011614803
- Cited by
- 83
- References
- 37
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 3 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 3.86
- Type
- journal article
- Language
- en
- Open access
- Locations
- The International Journal of Biochemistry & Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Key Research and Development Program of China
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- 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
- Keywords
- Drp1, pancreatic beta cells, beta-cell apoptosis, hyperglycemia, mitochondrial fission, cytochrome c release, mitochondrial membrane potential, caspase-3 activation, reactive oxygen species, diabetes pathogenesis, dominant-negative mutant
- MeSH terms
- Animals, Cell Line, Diabetes Mellitus, Type 2, Disease Models, Animal, Flow Cytometry, Glucose, Humans, Immunohistochemistry, Male, Microtubule-Associated Proteins, Rats, Wistar, Apoptosis, Reactive Oxygen Species, Reverse Transcriptase Polymerase Chain Reaction, In Situ Nick-End Labeling, GTP Phosphohydrolases, Mitochondrial Proteins, Dynamins, Cytochromes c, Microscopy, Electron, Transmission, Insulin-Secreting Cells, Rats, Caspase 3
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