ArticleDiabetes2017
Inhibition of 12/15-Lipoxygenase Protects Against β-Cell Oxidative Stress and Glycemic Deterioration in Mouse Models of Type 1 Diabetes.
Article in Diabetes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Wogonin attenuates septic cardiomyopathy by suppressing ALOX15-mediated ferroptosis.Acta pharmacologica Sinica · 2025Article
- Exercise-Stimulated Resolvin Biosynthesis in the Adipose Tissue Is Abrogated by High-Fat Diet-Induced Adrenergic Deficiency.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.JCI insight · 2024Article
- miR-146a-5p mediates inflammation-induced β cell mitochondrial dysfunction and apoptosis.The Journal of biological chemistry · 2024Article
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.bioRxiv : the preprint server for biology · 2024Article
- miR-146a-5p mediates inflammation-induced β cell mitochondrial dysfunction and apoptosis.bioRxiv : the preprint server for biology · 2024Article
- Genetic deletion of 12/15 lipoxygenase delays vascular remodeling and limits cardiorenal dysfunction after pressure overload.Journal of molecular and cellular cardiology plus · 2023Article
- A review on the relationship between Arachidonic acid 15-Lipoxygenase (ALOX15) and diabetes mellitus.PeerJ · 2023Review
- Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.Endocrinology · 2022Review
- Ferroptosis Signaling in Pancreatic β-Cells: Novel Insights & Therapeutic Targeting.International journal of molecular sciences · 2022Review
- 12/15-Lipoxygenase Regulation of Diabetic Cognitive Dysfunction Is Determined by Interfering with Inflammation and Cell Apoptosis.International journal of molecular sciences · 2022Article
- Effects of Inflammatory Factor Expression Regulated by 12/15 Lipoxygenase on Obesity-Related Nephropathy.Nutrients · 2022Article
- Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.Cell reports · 2022Article
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- 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
- Accurate Prediction of Inhibitor Binding to HIV-1 Protease Using CANDOCK.Frontiers in chemistry · 2021Article
- Gigantol ameliorates CClScientific reports · 2020Article
- Oxidative Stress in Cytokine-Induced Dysfunction of the Pancreatic Beta Cell: Known Knowns and Known Unknowns.Metabolites · 2020Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Islet β-cell dysfunction and aggressive macrophage activity are early features in the pathogenesis of type 1 diabetes (T1D). 12/15-Lipoxygenase (12/15-LOX) is induced in β-cells and macrophages during T1D and produces proinflammatory lipids and lipid peroxides that exacerbate β-cell dysfunction and macrophage activity. Inhibition of 12/15-LOX provides a potential therapeutic approach to prevent glycemic deterioration in T1D. Two inhibitors recently identified by our groups through screening efforts, ML127 and ML351, have been shown to selectively target 12/15-LOX with high potency. Only ML351 exhibited no apparent toxicity across a range of concentrations in mouse islets, and molecular modeling has suggested reduced promiscuity of ML351 compared with ML127. In mouse islets, incubation with ML351 improved glucose-stimulated insulin secretion in the presence of proinflammatory cytokines and triggered gene expression pathways responsive to oxidative stress and cell death. Consistent with a role for 12/15-LOX in promoting oxidative stress, its chemical inhibition reduced production of reactive oxygen species in both mouse and human islets in vitro. In a streptozotocin-induced model of T1D in mice, ML351 prevented the development of diabetes, with coincident enhancement of nuclear Nrf2 in islet cells, reduced β-cell oxidative stress, and preservation of β-cell mass. In the nonobese diabetic mouse model of T1D, administration of ML351 during the prediabetic phase prevented dysglycemia, reduced β-cell oxidative stress, and increased the proportion of anti-inflammatory macrophages in insulitis. The data provide the first evidence to date that small molecules that target 12/15-LOX can prevent progression of β-cell dysfunction and glycemic deterioration in models of T1D.
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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.