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Although 12\u2010LOX 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\u2014genetic manipulation and pharmacologic inhibition\u2014to interrogate the role of 12\u2010LOX in pancreatic development. Lipidomics analysis during zebrafish development demonstrated that 12\u2010LOX\u2010generated metabolites of arachidonic acid increase sharply during organogenesis stages, and that this increase is blocked by morpholino\u2010directed depletion of 12\u2010LOX. Furthermore, we found that either depletion or inhibition of 12\u2010LOX impairs both exocrine pancreas growth and unexpectedly, the generation of insulin\u2010producing \u03b2 cells. We demonstrate that morpholino\u2010mediated knockdown of GPR31, a purported G\u2010protein\u2010coupled receptor for 12\u2010HETE, largely phenocopies both the depletion and the inhibition of 12\u2010LOX. 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\u2010LOX in pancreatic organogenesis and islet formation, and additionally provide evidence that its effects are mediated via a signaling axis that includes the 12\u2010HETE receptor GPR31.<\/jats:p>","DOI":"10.1096\/fj.201902308rr","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T12:11:04Z","timestamp":1601035864000},"page":"14850-14862","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["A 12\u2010lipoxygenase\u2010Gpr31 signaling axis is required for pancreatic organogenesis in the zebrafish"],"prefix":"10.1096","volume":"34","author":[{"given":"Marimar","family":"Hernandez\u2010Perez","sequence":"first","affiliation":[{"name":"Department of Pediatrics Center for Diabetes and Metabolic Diseases Indiana University School of Medicine Indianapolis IN 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