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Genetic modulation of islet β-cell iPLA₂β expression provides evidence for its impact on β-cell apoptosis and autophagy.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Mitochondrial Homeostasis in Pancreatic β Cell Function: Mechanisms and Therapeutic Targets for Diabetes.Journal of diabetes · 2026Review
- Article
- Differential lipid signaling from CD4Frontiers in immunology · 2024Article
- Circulating Sphingolipids in Insulin Resistance, Diabetes and Associated Complications.International journal of molecular sciences · 2023Review
- CaProstaglandins & other lipid mediators · 2022Article
- Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLAMolecules (Basel, Switzerland) · 2021Article
- The Impact of the CaBiomolecules · 2021Review
- Article
- Review
- Macrophage polarization is linked to CaJournal of lipid research · 2020Article
- β-Lactones: A Novel Class of CaJournal of medicinal chemistry · 2019Article
- Amorphous solid dispersion of Berberine mitigates apoptosis via iPLAInternational journal of biological sciences · 2019Article
- The structure of iPLANature communications · 2018Article
- Polarization of Macrophages toward M2 Phenotype Is Favored by Reduction in iPLA2β (Group VIA Phospholipase A2).The Journal of biological chemistry · 2016Article
- Calcium-independent phospholipases A2 and their roles in biological processes and diseases.Journal of lipid research · 2015Review
- Group VIA Phospholipase A2 (iPLA2β) Modulates Bcl-x 5'-Splice Site Selection and Suppresses Anti-apoptotic Bcl-x(L) in β-Cells.The Journal of biological chemistry · 2015Article
- Inhibition of Ca2+-independent phospholipase A2β (iPLA2β) ameliorates islet infiltration and incidence of diabetes in NOD mice.Diabetes · 2015Article
- Roles and regulation of neutral sphingomyelinase-2 in cellular and pathological processes.Advances in biological regulation · 2015Review
- Evidence of contribution of iPLA2β-mediated events during islet β-cell apoptosis due to proinflammatory cytokines suggests a role for iPLA2β in T1D development.Endocrinology · 2014Article
- Dysfunctional mitochondrial bioenergetics and oxidative stress in Akita(+/Ins2)-derived β-cells.American journal of physiology. Endocrinology and metabolism · 2013Article
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9 authors at 3 institutions in 1 country.
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Abstract
β-cell apoptosis is a significant contributor to β-cell dysfunction in diabetes and ER stress is among the factors that contributes to β-cell death. We previously identified that the Ca²⁺-independent phospholipase A₂β (iPLA₂β), which in islets is localized in β-cells, participates in ER stress-induced β-cell apoptosis. Here, direct assessment of iPLA₂β role was made using β-cell-specific iPLA₂β overexpressing (RIP-iPLA₂β-Tg) and globally iPLA₂β-deficient (iPLA₂β-KO) mice. Islets from Tg, but not KO, express higher islet iPLA₂β and neutral sphingomyelinase, decrease in sphingomyelins, and increase in ceramides, relative to WT group. ER stress induces iPLA₂β, ER stress factors, loss of mitochondrial membrane potential (∆Ψ), caspase-3 activation, and β-cell apoptosis in the WT and these are all amplified in the Tg group. Surprisingly, β-cells apoptosis while reduced in the KO is higher than in the WT group. This, however, was not accompanied by greater caspase-3 activation but with larger loss of ∆Ψ, suggesting that iPLA₂β deficiency impacts mitochondrial membrane integrity and causes apoptosis by a caspase-independent manner. Further, autophagy, as reflected by LC3-II accumulation, is increased in Tg and decreased in KO, relative to WT. Our findings suggest that (1) iPLA₂β impacts upstream (UPR) and downstream (ceramide generation and mitochondrial) pathways in β-cells and (2) both over- or under-expression of iPLA₂β is deleterious to the β-cells. Further, we present for the first time evidence for potential regulation of autophagy by iPLA₂β in islet β-cells. These findings support the hypothesis that iPLA₂β induction under stress, as in diabetes, is a key component to amplifying β-cell death processes.
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