Mitochondrial function in normal and diabetic β-cells
Open accessAbstract
The aetiology of type 2, or non-insulin-dependent, diabetes mellitus has been characterized in only a limited number of cases. Among these, mitochondrial diabetes, a rare subform of the disease, is the consequence of pancreatic beta-cell dysfunction caused by mutations in mitochondrial DNA, which is distinct from the nuclear genome. The impact of such mutations on beta-cell function reflects the importance of mitochondria in the control of insulin secretion. The beta-cell mitochondria serve as fuel sensors, generating factors that couple nutrient metabolism to the exocytosis of insulin-containing vesicles. The latter process requires an increase in cytosolic Ca2+, which depends on ATP synthesized by the mitochondria. This organelle also generates other factors, of which glutamate has been proposed as a potential intracellular messenger.
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β-cell lines in which mitochondria have been removed fail to release insulin in response to glucose, and reintroduction of normal mitochondria restores normal insulin secretion.
“Similarly, β-cell lines in which mitochondria have been removed (rho-0 cells) fail to release insulin in response to glucose stimulation, and reintroduction of normal mitochondria restores normal insulin secretion (418).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [418]
In “Mitochondrial dysfunction in the β-cell,” the paper says rho-0 β-cell lines lack glucose-induced insulin release and that replenishing them with normal mitochondria restores the response. But it describes depletion of mitochondrial DNA, not removal of the mitochondria themselves; it also does not specify that secretion returns to a normal level. (LLM, conf=0.88)
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- Authors
- Maechler, P., & Wollheim, C. B.
- Affiliations
- University of Geneva (CH)
- Corresponding author
- Maechler, Pierre
- Wollheim, Claes B.
- Venue
- Nature
- Published
- 2001-12
- Volume
- 414
- Issue
- 6865
- Pages
- 807-812
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2030845275
- Cited by
- 519
- References
- 5
- Citations by year
- 2026: 10 · 2025: 10 · 2024: 13 · 2023: 16 · 2022: 25 · 2021: 17 · 2020: 19 · 2019: 12 · 2018: 8 · 2017: 21 · 2016: 12 · 2015: 29 · 2014: 22 · 2013: 29 · 2012: 27
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- RePEc: Research Papers in Economics (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- 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 › Genetics › Diabetes and associated disorders
- Keywords
- mitochondrial function, pancreatic beta cells, type 2 diabetes, mitochondrial diabetes, mitochondrial DNA mutations, insulin secretion, nutrient sensing, ATP, intracellular calcium, exocytosis, glutamate, intracellular signaling
- MeSH terms
- Insulin Secretion, Animals, Diabetes Mellitus, Type 2, DNA, Mitochondrial, Exocytosis, Humans, Insulin, Islets of Langerhans, Mitochondria, Mutation, Signal Transduction, Mitochondrial Diseases
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