ArticleDiabetes2008
Nonobese diabetic (NOD) mice congenic for a targeted deletion of 12/15-lipoxygenase are protected from autoimmune diabetes.
Article in Diabetes, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 96 citations in OpenAlex.
- Messenger RNA delivery to islet β cells using conjugated lipid nanoparticles.Cell reports. Medicine · 2026Article
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.JCI insight · 2024Article
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.bioRxiv : the preprint server for biology · 2024Article
- Functional Characterization of Transgenic Mice Overexpressing Human 15-Lipoxygenase-1 (ALOX15) under the Control of the aP2 Promoter.International journal of molecular sciences · 2023Article
- A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus.PeerJ · 2023Review
- Male infertility and somatic health - insights into lipid damage as a mechanistic link.Nature reviews. Urology · 2022Review
- Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.Cell reports · 2022Article
- Review
- Inonotus obliquus polysaccharide ameliorates serum profiling in STZ-induced diabetic mice model.BMC chemistry · 2021Article
- Syntaxin 4 Enrichment in β-Cells Prevents Conversion to Autoimmune Diabetes in Non-Obese Diabetic (NOD) Mice.Diabetes · 2021Article
- Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLAMolecules (Basel, Switzerland) · 2021Article
- 12-Lipoxygenase governs the innate immune pathogenesis of islet inflammation and autoimmune diabetes.JCI insight · 2021Article
- Lipoxygenase inhibitor ML351 dysregulated an innate inflammatory response leading to impaired cardiac repair in acute heart failure.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Regulation of Tissue Inflammation by 12-Lipoxygenases.Biomolecules · 2021Review
- The Impact of the CaBiomolecules · 2021Review
- Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.Signal transduction and targeted therapy · 2021Review
- A 12-lipoxygenase-Gpr31 signaling axis is required for pancreatic organogenesis in the zebrafish.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Hypusinated eIF5A is expressed in the pancreas and spleen of individuals with type 1 and type 2 diabetes.PloS one · 2020Article
- Platelet-type 12-lipoxygenase deletion provokes a compensatory 12/15-lipoxygenase increase that exacerbates oxidative stress in mouse islet β cells.The Journal of biological chemistry · 2019Article
- Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.Pharmacology & therapeutics · 2019Review
5 more citing papers are in PubMed but not listed here.
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13 authors at 1 institution in 1 country.
Funding
Abstract
objective12/15-lipoxygenase (12/15-LO), one of a family of fatty acid oxidoreductase enzymes, reacts with polyenoic fatty acids to produce proinflammatory lipids. 12/15-LO is expressed in macrophages and pancreatic beta-cells. It enhances interleukin 12 production by macrophages, and several of its products induce apoptosis of beta-cells at nanomolar concentrations in vitro. We had previously demonstrated a role for 12/15-LO in beta-cell damage in the streptozotocin model of diabetes. Since the gene encoding 12/15-LO (gene designation Alox15) lies within the Idd4 diabetes susceptibility interval in NOD mice, we hypothesized that 12/15-LO is also a key regulator of diabetes susceptibility in the NOD mouse. RESEARCH DESIGN AND
methodsWe developed NOD mice carrying an inactivated 12/15-LO locus (NOD-Alox15(null)) using a "speed congenic" protocol, and the mice were monitored for development of insulitis and diabetes.
resultsNOD mice deficient in 12/15-LO develop diabetes at a markedly reduced rate compared with NOD mice (2.5 vs. >60% in females by 30 weeks). Nondiabetic female NOD-Alox15(null) mice demonstrate improved glucose tolerance, as well as significantly reduced severity of insulitis and improved beta-cell mass, when compared with age-matched nondiabetic NOD females. Disease resistance is associated with decreased numbers of islet-infiltrating activated macrophages at 4 weeks of age in NOD-Alox15(null) mice, preceding the development of insulitis. Subsequently, islet-associated infiltrates are characterized by decreased numbers of CD4(+) T cells and increased Foxp3(+) cells.
conclusionsThese results suggest an important role for 12/15-LO in conferring susceptibility to autoimmune diabetes in NOD mice through its effects on macrophage recruitment or activation.
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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.