Dobrian, A. D.Morris, M. A.Taylor-Fishwick, D. A.Holman, T. R.Imai, Y.Mirmira, Raghu G.Nadler, J. L.2018-11-202018-11-202019-03Dobrian, A. D., Morris, M. A., Taylor-Fishwick, D. A., Holman, T. R., Imai, Y., Mirmira, R. G., & Nadler, J. L. (2019). Role of the 12-Lipoxygenase Pathway in Diabetes Pathogenesis and Complications. Pharmacology & Therapeutics, 195, 100–110. https://doi.org/10.1016/j.pharmthera.2018.10.010https://hdl.handle.net/1805/1779512-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro- and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly and positively impact health outcomes of patients living with both type 1 and type 2 diabetes. To date, the development of truly specific and efficacious inhibitors has been hampered by homology of LOX family members; however, improvements in high throughput screening have improved the inhibitor landscape. Here, we describe the function and role of human 12-LOX, and mouse 12-LOX and 12/15-LOX, in the development of diabetes and diabetes-related complications, and describe promise in the development of strategies to limit pro-inflammatory metabolites, primarily via new small molecule 12-LOX inhibitors.enPublisher Policylipoxygenasetype 1 diabetestype 2 diabetes-related complicationsArticle