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,
Diabetologia. 2015 Mar;58(3):425-8. doi: 10.1007/s00125-014-3482-7. Epub 2014 Dec 24.
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.
炎症是 1 型和 2 型糖尿病中胰岛的一种病理特征，导致胰岛内分泌细胞衰竭，并导致这两种疾病发生高血糖。事实上，最近已经发现许多免疫靶标在 2 型糖尿病中发生改变，但很少有靶标被转化为临床应用。Taylor-Fishwick 及其同事通过进行概念验证研究，旨在改变这种状况，研究在暴露于促炎细胞因子的啮齿动物和人β细胞中，小分子 12-脂氧合酶抑制剂的疗效。这些研究的结果发表在本期的《糖尿病学》杂志上（DOI: 10.1007/s00125-014-3452-0），其建立在大量的临床前数据基础上，这些数据表明 12-脂氧合酶在 1 型和 2 型糖尿病的啮齿动物模型中起作用。虽然关于细胞因子如何调节 12-脂氧合酶的激活以及激活的下游后果，仍存在一些未解决的机制问题，但人们希望未来使用新鉴定的选择性抑制剂的研究可以克服这项研究的体外局限性，并允许这些非常有趣的发现最终在临床上得到转化。
