Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes
Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes
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DOI：
10.2337/diabetes.54.suppl_2.s73
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发表时间：
2005-12-01
期刊：
影响因子：
7.7
通讯作者：
Hotamisligil, GS
中科院分区：
文献类型：
--
作者：
Hotamisligil, GS
新陈代谢和免疫系统是最基本的生存要求，许多新陈代谢和免疫反应途径或营养和病原体传感系统在进化上高度保守。因此，代谢和免疫途径也是高度整合和相互依赖的。在过去的十年中，很明显，这种界面在慢性代谢性疾病的发病机制中发挥了关键作用，特别是肥胖症和2型糖尿病。重要的是，随着炎症介质如肿瘤坏死因子α和胰岛素受体信号之间因果联系的发现，以及潜在的分子机制的阐明，如c-Jun NH2末端激酶(JNK)和核因子-kappa B激酶的抑制物，抑制胰岛素作用的转录和翻译后修饰，肥胖和糖尿病的炎症成分现在得到了牢固的确立。最近，肥胖诱导的内质网应激被证明是肥胖诱导的JNK激活、炎症反应和外周胰岛素抵抗产生的基础。本文将回顾应激、炎症和代谢性疾病之间的联系，特别是2型糖尿病，并通过集中于JNK和内质网应激反应来讨论从这个平台出现的机制和治疗机会。
Metabolic and immune systems are the most fundamental requirements for survival, and many metabolic and immune response pathways or nutrient- and pathogen-sensing systems have been evolutionarily highly conserved. Consequently, metabolic and immune pathways are also highly integrated and interdependent. In the past decade, it became apparent that this interface plays a critical role in the pathogenesis of chronic metabolic diseases, particularly obesity and type 2 diabetes. Importantly, the inflammatory component in obesity and diabetes is now firmly established with the discovery of causal links between inflammatory mediators, such as tumor necrosis factor (TNF)-alpha and insulin receptor signaling and the elucidation of the underlying molecular mechanisms, such as c-Jun NH2-terminal kinase (JNK)- and inhibitor of nuclear factor-kappa B kinase-mediated transcriptional and posttranslational modifications that inhibit insulin action. More recently, obesity-induced endoplasmic reticulum stress has been demonstrated to underlie the initiation of obesity-induced JNK activation, inflammatory responses, and generation of peripheral insulin resistance. This article will review the link between stress, inflammation, and metabolic disease, particularly type 2 diabetes, and discuss the mechanistic and therapeutic opportunities that emerge from this platform by focusing on JNK and endoplasmic reticulum stress responses.