Akademska digitalna zbirka SLovenije - logo
E-viri
Recenzirano Odprti dostop
  • Role of the 12-lipoxygenase...
    Dobrian, A.D.; Morris, M.A.; Taylor-Fishwick, D.A.; Holman, T.R.; Imai, Y.; Mirmira, R.G.; Nadler, J.L.

    Pharmacology & therapeutics (Oxford), 03/2019, Letnik: 195
    Journal Article

    12-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.