花生四烯酸
脂氧合酶
2型糖尿病
糖尿病
炎症
花生四烯酸5-脂氧合酶
基因亚型
酶
发病机制
花生四烯酸代谢
生物化学
化学
药理学
医学
内分泌学
内科学
基因
作者
Anca D. Dobrian,Margaret A. Morris,David A. Taylor‐Fishwick,Theodore R. Holman,Yumiko Imai,Raghavendra G. Mirmira,Jerry L. Nadler
标识
DOI:10.1016/j.pharmthera.2018.10.010
摘要
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.
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