title: Targeting 12-lipoxygenase as a novel strategy to combat the effects of inflammation on beta cells in diabetes.
abstract: Inflammation is a pathological feature of the pancreatic islet in type 1 and 2 diabetes, contributing to islet endocrine cell failure and the onset of hyperglycaemia in both diseases. Indeed, numerous immune targets have recently been found to be altered in type 2 diabetes, but few have yet to be translated to the clinic. Taylor-Fishwick and colleagues aimed to change this by performing proof-of-concept studies investigating the efficacy of small molecule inhibitors of 12-lipoxygenase in rodent and human beta cells exposed to proinflammatory cytokines. The results of these studies, published in this issue of Diabetologia (DOI: 10.1007/s00125-014-3452-0), build on a wealth of preclinical data that have implicated 12-lipoxygenase in rodent models of type 1 and 2 diabetes. While there remain some unanswered mechanistic questions regarding how cytokines regulate 12-lipoxygenase activation and the downstream consequences of activation, it is hoped that future studies with newly identified selective inhibitors may overcome the in vitro limitations of this study and allow for the eventual clinical translation of these highly interesting findings.
authors.affiliation: Faculty of Medicine, Department of Surgery and Department of Cellular & Physiological Sciences, The University of British Columbia, Child & Family Research Institute, Room A4-183, 950W 28th Avenue, Vancouver, BC, Canada, V5Z 4H4, ehses@mail.ubc.ca.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Ehses
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism*; D008297:Male
chemical_list: D004791:Enzyme Inhibitors; D001092:Arachidonate 12-Lipoxygenase