ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2020
A 12-lipoxygenase-Gpr31 signaling axis is required for pancreatic organogenesis in the zebrafish.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- Integrated screening identifies GPR31 as a key driver and druggable target for metabolic dysfunction-associated steatohepatitis.The Journal of clinical investigation · 2025Article
- 12-Lipoxygenase Inhibition Improves Glycemia and Obesity-associated Inflammation in Male Human Gene Replacement Mice.Endocrinology · 2025Article
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.JCI insight · 2024Article
- The pyruvate-GPR31 axis promotes transepithelial dendrite formation in human intestinal dendritic cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- 12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice.bioRxiv : the preprint server for biology · 2024Article
- Illuminating the druggable genome: Pathways to progress.Drug discovery today · 2024Review
- Membrane Lipid Derivatives: Roles of Arachidonic Acid and Its Metabolites in Pancreatic Physiology and Pathophysiology.Molecules (Basel, Switzerland) · 2023Review
- Therapeutic Strategies Targeting Pancreatic Islet β-Cell Proliferation, Regeneration, and Replacement.Endocrinology · 2022Article
- Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.Endocrinology · 2022Review
- Extracellular vesicles in β cell biology: Role of lipids in vesicle biogenesis, cargo, and intercellular signaling.Molecular metabolism · 2022Review
- Role of Polyamines and Hypusine in β Cells and Diabetes Pathogenesis.Metabolites · 2022Review
- Review
- A Novel 2-Hit Zebrafish Model to Study Early Pathogenesis of Non-Alcoholic Fatty Liver Disease.Biomedicines · 2022Article
- Review
- 12-Lipoxygenase governs the innate immune pathogenesis of islet inflammation and autoimmune diabetes.JCI insight · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
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Abstract
12-Lipoxygenase (12-LOX) is a key enzyme in arachidonic acid metabolism, and alongside its major product, 12-HETE, plays a key role in promoting inflammatory signaling during diabetes pathogenesis. Although 12-LOX is a proposed therapeutic target to protect pancreatic islets in the setting of diabetes, little is known about the consequences of blocking its enzymatic activity during embryonic development. Here, we have leveraged the strengths of the zebrafish-genetic manipulation and pharmacologic inhibition-to interrogate the role of 12-LOX in pancreatic development. Lipidomics analysis during zebrafish development demonstrated that 12-LOX-generated metabolites of arachidonic acid increase sharply during organogenesis stages, and that this increase is blocked by morpholino-directed depletion of 12-LOX. Furthermore, we found that either depletion or inhibition of 12-LOX impairs both exocrine pancreas growth and unexpectedly, the generation of insulin-producing β cells. We demonstrate that morpholino-mediated knockdown of GPR31, a purported G-protein-coupled receptor for 12-HETE, largely phenocopies both the depletion and the inhibition of 12-LOX. Moreover, we show that loss of GPR31 impairs pancreatic bud fusion and pancreatic duct morphogenesis. Together, these data provide new insight into the requirement of 12-LOX in pancreatic organogenesis and islet formation, and additionally provide evidence that its effects are mediated via a signaling axis that includes the 12-HETE receptor GPR31.
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Registered trials
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