Journal article
Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications
Pharmacology & therapeutics (Oxford), Vol.195, pp.100-110
03/2019
DOI: 10.1016/j.pharmthera.2018.10.010
PMCID: PMC6397662
PMID: 30347209
Abstract
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.
Details
- Title: Subtitle
- Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications
- Creators
- A.D. Dobrian - Eastern Virginia Medical SchoolM.A. Morris - Eastern Virginia Medical SchoolD.A. Taylor-Fishwick - Eastern Virginia Medical SchoolT.R. Holman - University of California, Santa CruzY. Imai - University of IowaR.G. Mirmira - Indiana UniversityJ.L. Nadler - Eastern Virginia Medical School
- Resource Type
- Journal article
- Publication Details
- Pharmacology & therapeutics (Oxford), Vol.195, pp.100-110
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.pharmthera.2018.10.010
- PMID
- 30347209
- PMCID
- PMC6397662
- ISSN
- 0163-7258
- eISSN
- 1879-016X
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01-DK105588-01; DOI: 10.13039/100000002, name: National Institutes of Health, award: R15H114062; DOI: 10.13039/100000002, name: National Institutes of Health, award: R01-DK090490
- Language
- English
- Date published
- 03/2019
- Academic Unit
- Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984359947702771
Metrics
14 Record Views