ArticleDiabetes2015
Inhibition of Ca2+-independent phospholipase A2β (iPLA2β) ameliorates islet infiltration and incidence of diabetes in NOD mice.
Article in Diabetes, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
32 citing papers in PubMed, 51 citations in OpenAlex.
- Distinct Roles of Myeloid- and Hepatocyte-PLA2G6 Deletion in Mice With Metabolic Dysfunction-Associated Steatotic Liver Disease.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Liver-Specific Suppression of PLA2G6/iPLAFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- The mechanism of allosteric regulation of calcium-independent phospholipase AProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis.Cell communication and signaling : CCS · 2024Article
- Differential lipid signaling from CD4Frontiers in immunology · 2024Article
- Lysophosphatidylserine induces necrosis in pressure overloaded male mouse hearts via G protein coupled receptor 34.Nature communications · 2023Article
- Article
- The oxylipin profile is associated with development of type 1 diabetes: the Diabetes Autoimmunity Study in the Young (DAISY).Diabetologia · 2021Article
- The Impact of the CaBiomolecules · 2021Review
- Choline Glycerophospholipid-Derived Prostaglandins Attenuate TNFα Gene Expression in Macrophages via a cPLACells · 2021Article
- Metabolic Effects of Selective Deletion of Group VIA Phospholipase ABiomolecules · 2020Article
- Rescue of Hepatic Phospholipid Remodeling Defectin iPLA2β-Null Mice Attenuates Obese but Not Non-Obese Fatty Liver.Biomolecules · 2020Review
- Article
- The Contribution of Cytosolic Group IVA and Calcium-Independent Group VIA Phospholipase ABiomolecules · 2020Article
- 2-Oxoester Phospholipase ABiomolecules · 2020Article
- Macrophage polarization is linked to CaJournal of lipid research · 2020Article
- Reduced Acoustic Startle Response and Prepulse Inhibition in the Tg4-42 Model of Alzheimer's Disease.Journal of Alzheimer's disease reports · 2019Article
- Small-molecule inhibitors as potential therapeutics and as tools to understand the role of phospholipases ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- iPLABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Autoimmune β-cell death leads to type 1 diabetes, and with findings that Ca(2+)-independent phospholipase A2β (iPLA2β) activation contributes to β-cell death, we assessed the effects of iPLA2β inhibition on diabetes development. Administration of FKGK18, a reversible iPLA2β inhibitor, to NOD female mice significantly reduced diabetes incidence in association with 1) reduced insulitis, reflected by reductions in CD4(+) T cells and B cells; 2) improved glucose homeostasis; 3) higher circulating insulin; and 4) β-cell preservation. Furthermore, FKGK18 inhibited production of tumor necrosis factor-α (TNF-α) from CD4(+) T cells and antibodies from B cells, suggesting modulation of immune cell responses by iPLA2β-derived products. Consistent with this, 1) adoptive transfer of diabetes by CD4(+) T cells to immunodeficient and diabetes-resistant NOD.scid mice was mitigated by FKGK18 pretreatment and 2) TNF-α production from CD4(+) T cells was reduced by inhibitors of cyclooxygenase and 12-lipoxygenase, which metabolize arachidonic acid to generate bioactive inflammatory eicosanoids. However, adoptive transfer of diabetes was not prevented when mice were administered FKGK18-pretreated T cells or when FKGK18 administration was initiated with T-cell transfer. The present observations suggest that iPLA2β-derived lipid signals modulate immune cell responses, raising the possibility that early inhibition of iPLA2β may be beneficial in ameliorating autoimmune destruction of β-cells and mitigating type 1 diabetes development.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.