ArticleDiabetologia2015
Selective inhibition of 12-lipoxygenase protects islets and beta cells from inflammatory cytokine-mediated beta cell dysfunction.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- Ferroptosis Signaling in Pancreatic β-Cells: Novel Insights & Therapeutic Targeting.International journal of molecular sciences · 2022Review
- Review
- Lipidomic Profiling of Bronchoalveolar Lavage Fluid Extracellular Vesicles Indicates Their Involvement in Lipopolysaccharide-Induced Acute Lung Injury.Journal of innate immunity · 2022Article
- 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
- Therapy to Obese Type 2 Diabetes Mellitus: How Far Will We Go Down the Wrong Road?Chinese journal of integrative medicine · 2020Review
- Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.Pharmacology & therapeutics · 2019Review
- Targeting Type 1 Diabetes: Selective Approaches for New Therapies.Biochemistry · 2019Review
- Article
- Fatty Acid-Stimulated Insulin Secretion vs. Lipotoxicity.Molecules (Basel, Switzerland) · 2018Review
- Article
- 12-Lipoxygenase Inhibitor Improves Functions of Cytokine-Treated Human Islets and Type 2 Diabetic Islets.The Journal of clinical endocrinology and metabolism · 2017Article
- Interaction of 12/15-lipoxygenase with fatty acids alters the leukocyte kinetics leading to improved postmyocardial infarction healing.American journal of physiology. Heart and circulatory physiology · 2017Article
- Developmental Role of Macrophage Cannabinoid-1 Receptor Signaling in Type 2 Diabetes.Diabetes · 2017Article
- 12-HETER1/GPR31, a high-affinity 12(S)-hydroxyeicosatetraenoic acid receptor, is significantly up-regulated in prostate cancer and plays a critical role in prostate cancer progression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Lipids and immunoinflammatory pathways of beta cell destruction.Diabetologia · 2016Review
- Calcium-independent phospholipases A2 and their roles in biological processes and diseases.Journal of lipid research · 2015Review
- Minireview: 12-Lipoxygenase and Islet β-Cell Dysfunction in Diabetes.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Targeting 12-lipoxygenase as a novel strategy to combat the effects of inflammation on beta cells in diabetes.Diabetologia · 2015Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
aims/hypothesisIslet inflammation leads to loss of functional pancreatic beta cell mass. Increasing evidence suggests that activation of 12-lipoxygenase leads to inflammatory beta cell loss. This study evaluates new specific small-molecule inhibitors of 12-lipoxygenase for protecting rodent and human beta cells from inflammatory damage.
methodsMouse beta cell lines and mouse and human islets were treated with inflammatory cytokines IL-1β, TNFα and IFNγ in the absence or presence of novel selective 12-lipoxygenase inhibitors. Glucose-stimulated insulin secretion (GSIS), gene expression, cell survival and 12-S-hydroxyeicosatetraenoic acid (12-S-HETE) levels were evaluated using established methods. Pharmacokinetic analysis was performed with the lead inhibitor in CD1 mice.
resultsInflammatory cytokines led to the loss of human beta cell function, elevated cell death, increased inflammatory gene expression and upregulation of 12-lipoxygenase expression and activity (measured by 12-S-HETE generation). Two 12-lipoxygenase inhibitors, Compounds 5 and 9, produced a concentration-dependent reduction of stimulated 12-S-HETE levels. GSIS was preserved in the presence of the 12-lipoxygenase inhibitors. 12-Lipoxygenase inhibition preserved survival of primary mouse and human islets. When administered orally, Compound 5 reduced plasma 12-S-HETE in CD1 mice. Compounds 5 and 9 preserved the function and survival of human donor islets exposed to inflammatory cytokines. CONCLUSIONS/
interpretationSelective inhibition of 12-lipoxygenase activity confers protection to beta cells during exposure to inflammatory cytokines. These concept validation studies identify 12-lipoxygenase as a promising target in the prevention of loss of functional beta cells in diabetes.
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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.