JNK at the crossroad of obesity, insulin resistance, and cell stress response.
JNK at the crossroad of obesity, insulin resistance, and cell stress response.
复制标题
JNK在肥胖，胰岛素抵抗和细胞应激反应的十字路口处。
DOI：
10.1016/j.molmet.2016.12.001
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发表时间：
2017-02
影响因子：
8.1
通讯作者：
Becattini B
中科院分区：
文献类型：
--
作者：
Solinas G;Becattini B
CJun-N-末端激酶(JNK)在细胞应激反应中发挥核心作用，其结果从细胞死亡到细胞增殖和存活，取决于特定的背景。JNK也是肥胖和胰岛素抵抗中被研究最多的信号转导分子之一，研究发现了肥胖和胰岛素抵抗之间的新的分子机制。新的证据表明，虽然JNK1和JNK2亚型促进肥胖和胰岛素抵抗的发展，但JNK3的活性可以防止过度肥胖。此外，目前的证据表明，在疾病进展的特定阶段，特定细胞类型中的JNK活性可能会促进细胞对与肥胖和2型糖尿病相关的应激反应的耐受。这篇综述提供了关于JNK在从肥胖到胰岛素抵抗、NAFLD、2型糖尿病和糖尿病并发症进展中的作用的当前文献的概述。虽然目前的证据表明，抑制JNK1/2可以改善肥胖患者的胰岛素敏感性，但JNK在从胰岛素抵抗到糖尿病及其并发症的进展中的作用在很大程度上尚未解决。更好地了解JNK在肥胖和2型糖尿病应激反应中的作用，以及开发具有特定组织分布的异构体特异性抑制物，将是开发JNK作为治疗2型糖尿病的可能药物靶点所必需的。
The cJun-N-terminal-kinase (JNK) plays a central role in the cell stress response, with outcomes ranging from cell death to cell proliferation and survival, depending on the specific context. JNK is also one of the most investigated signal transducers in obesity and insulin resistance, and studies have identified new molecular mechanisms linking obesity and insulin resistance. Emerging evidence indicates that whereas JNK1 and JNK2 isoforms promote the development of obesity and insulin resistance, JNK3 activity protects from excessive adiposity. Furthermore, current evidence indicates that JNK activity within specific cell types may, in specific stages of disease progression, promote cell tolerance to the stress associated with obesity and type-2 diabetes. This review provides an overview of the current literature on the role of JNK in the progression from obesity to insulin resistance, NAFLD, type-2 diabetes, and diabetes complications. Whereas current evidence indicates that JNK1/2 inhibition may improve insulin sensitivity in obesity, the role of JNK in the progression from insulin resistance to diabetes, and its complications is largely unresolved. A better understanding of the role of JNK in the stress response to obesity and type-2 diabetes, and the development of isoform-specific inhibitors with specific tissue distribution will be necessary to exploit JNK as possible drug target for the treatment of type-2 diabetes.