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Increased Vulnerability of Brain Mitochondria in Diabetic (Goto-Kakizaki) Rats With Aging and Amyloid-β Exposure
Open accessAbstract
This study evaluated the respiratory indexes (respiratory control ratio [RCR] and ADP/O ratio), mitochondrial transmembrane potential (ΔΨm), repolarization lag phase, repolarization level, ATP/ADP ratio, and induction of the permeability transition pore of brain mitochondria isolated from normal Wistar and GK diabetic rats of different ages (1.5, 12, and 24 months of age). The effect of amyloid β-peptides, 50 μmol/l Aβ25–35 or 2 μmol/l Aβ1–40, on mitochondrial function was also analyzed. Aging of diabetic mice induced a decrease in brain mitochondrial RCR, ADP/O, and ATP/ADP ratios but induced an increase in the repolarization lag phase. Brain mitochondria from older diabetic rats were more prone to the induction of the permeability transition pore, i.e., mitochondria from 24-month-old diabetic rats accumulated much less Ca2+ (20 μmol/l) than those isolated from 12-month-old rats (50 μmol/l) or 1.5-month-old rats (100 μmol/l). In the presence of 50 μmol/l Aβ25–35 or 2 μmol/l Aβ1–40, age-related mitochondrial effects were potentiated. These results indicate that diabetes-related mitochondrial dysfunction is exacerbated by aging and/or by the presence of neurotoxic agents such as amyloid β-peptides, supporting the idea that diabetes and aging are risk factors for the neurodegeneration induced by these peptides.
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“Furthermore, a mitochondrial injury may play a role in transitioning from diabetes to AD, as exposing diabetic rats’ brain mitochondria to Aβ increases their vulnerability. 105”
From Anti-inflammatory role of glucagon-like peptide 1 receptor agonists and its clinical implications (2024) · cites this paper as [105]
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Metadata
- Authors
- Moreira, P. I., Santos, M. S., Moreno, A. M., Seiça, R., & Oliveira, C. R.
- Affiliations
- University of Coimbra (PT)
- Center for Neuroscience of Coimbra, Department of Zoology, University of Coimbra, Coimbra, Portugal
- Faculty of Medicine, University of Coimbra, Coimbra, Portugal
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2003-06-01
- Volume
- 52
- Issue
- 6
- Pages
- 1449-1456
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2119876958
- Cited by
- 117
- References
- 54
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 1 · 2019: 7 · 2018: 8 · 2017: 9 · 2016: 7 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 9
- FWCI
- 2.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- brain mitochondria, mitochondrial dysfunction, aging, amyloid-beta, Goto-Kakizaki rats, mitochondrial permeability transition pore, mitochondrial membrane potential, respiratory control ratio, ADP/O ratio, ATP/ADP ratio, calcium accumulation, neurodegeneration, Alzheimer's disease
- MeSH terms
- Adenine Nucleotides, Aging, Animals, Brain, Diabetes Mellitus, Type 2, Glycated Hemoglobin, Membrane Potentials, Mitochondria, Oxygen Consumption, Rats, Mutant Strains, Reference Values, Amyloid beta-Peptides, Rats, Wistar, Rats
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