Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada.
Mediators Inflamm. 2010;2010:359732. doi: 10.1155/2010/359732. Epub 2010 May 18.
Diabetes and obesity are chronic conditions associated with elevated oxidative/inflammatory activities with a continuum of tissue insults leading to more severe cardiometabolic and renal complications including myocardial infarction and end-stage-renal damage. A common denominator of these chronic conditions is the enhanced the levels of cytokines like tumour necrosis factor-alpha (TNF-alpha), interleukin (IL-6), IL-1beta and resistin, which in turn activates the c-Jun-N-terminal kinase (JNK) and NF-kappaB pathways, creating a vicious cycle that exacerbates insulin resistance, type-2 diabetes and related complications. Emerging evidence indicates that heme oxygenase (HO) inducers are endowed with potent anti-diabetic and insulin sensitizing effects besides their ability to suppress immune/inflammatory response. Importantly, the HO system abates inflammation through several mechanisms including the suppression of macrophage-infiltration and abrogation of oxidative/inflammatory transcription factors like NF-kappaB, JNK and activating protein-1. This review highlights the mechanisms by which the HO system potentiates insulin signalling, with particular emphasis on HO-mediated suppression of oxidative and inflammatory insults. The HO system could be explored in the search for novel remedies against cardiometabolic diseases and their complications.
糖尿病和肥胖是与氧化/炎症活性升高相关的慢性疾病，其组织损伤呈连续谱，导致更严重的心血管代谢和肾脏并发症，包括心肌梗死和终末期肾脏损害。这些慢性疾病的一个共同特征是细胞因子水平升高，如肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-6）、IL-1β和抵抗素，而这些细胞因子反过来又激活了 c-Jun-N 末端激酶（JNK）和 NF-κB 途径，形成一个恶性循环，加剧胰岛素抵抗、2 型糖尿病和相关并发症。新出现的证据表明，血红素加氧酶（HO）诱导剂除了具有抑制免疫/炎症反应的能力外，还具有很强的抗糖尿病和胰岛素增敏作用。重要的是，HO 系统通过多种机制减轻炎症，包括抑制巨噬细胞浸润和阻断核因子-κB、JNK 和激活蛋白-1 等氧化/炎症转录因子。本文重点介绍了 HO 系统增强胰岛素信号转导的机制，特别强调了 HO 介导的氧化和炎症损伤的抑制作用。HO 系统可能在寻找针对心血管代谢疾病及其并发症的新疗法方面得到探索。
