The sensitivity of pancreatic β-cells to mitochondrial injuries triggered by lipotoxicity and oxidative stress.
Open accessAbstract
Pancreatic beta-cells are essential for the maintenance of glucose homoeostasis, and dysfunction of these insulin-secreting cells results in the development of diabetes. In the course of events leading from obesity to Type 2 diabetes, several mechanisms are currently envisaged. Among them, lipids and oxidative stress are considered as toxic candidates for the beta-cell. The cellular link between fatty acids and ROS (reactive oxygen species) is essentially the mitochondrion, a key organelle for the control of insulin secretion. Mitochondria are the main source of ROS and are also the primary target of oxidative attacks. The present review presents the current knowledge of lipotoxicity related to oxidative stress in the context of mitochondrial function in the beta-cell.
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Nonesterified fatty acids associated with obesity and type 2 diabetes may impair islet function by mechanisms including fatty acid-induced apoptosis, malonyl-CoA accumulation, cytoplasmic fatty acyl-CoA accumulation, decreased insulin gene transcription, and ROS induction.
“Nonesterified fatty acids associated with obesity and type 2 diabetes may impair islet function by several mechanisms, as recently reviewed (194). These include fatty acid–induced apoptosis, accumulation of malonyl-CoA, and consequent accumulation of cytoplasmic fatty acyl-CoA molecules, decreased insulin gene transcription, and induction of ROS.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [194]
Low levels of ROS are necessary for insulin secretion, but chronic, high mitochondrial ROS production can have a deleterious effect on β-cell function.
“Low levels of ROS are necessary for insulin secretion, but chronic, high mitochondrial ROS production can have a deleterious effect on -cell function (254 -256).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [254]
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- Authors
- Li, N., Frigerio, F., & Maechler, P.
- Affiliations
- University of Geneva (CH)
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2008-09-19
- Volume
- 36
- Issue
- 5
- Pages
- 930-934
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- OpenAlex
- W1990045305
- Cited by
- 114
- References
- 65
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 7 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 3 · 2016: 8 · 2015: 4 · 2014: 8 · 2013: 4 · 2012: 11
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- Licence
- cc-by
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- pancreatic beta cells, lipotoxicity, oxidative stress, mitochondrial dysfunction, reactive oxygen species, insulin secretion, type 2 diabetes, obesity, fatty acids, glucose homeostasis
- MeSH terms
- Animals, Diabetes Mellitus, DNA, Mitochondrial, Humans, Lipids, Mitochondria, Reactive Oxygen Species, Oxidative Stress, Insulin-Secreting Cells
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