Inflammation Improves Glucose Homeostasis through IKKβ-XBP1s Interaction.
Inflammation Improves Glucose Homeostasis through IKKβ-XBP1s Interaction.
复制标题
DOI：
10.1016/j.cell.2016.10.015
复制
发表时间：
2016-11-03
期刊：
影响因子：
64.5
通讯作者：
Ozcan U
中科院分区：
文献类型：
--
作者：
Liu J;Ibi D;Taniguchi K;Lee J;Herrema H;Akosman B;Mucka P;Salazar Hernandez MA;Uyar MF;Park SW;Karin M;Ozcan U
人们普遍认为，与肥胖相关的炎症在2型糖尿病的发展中具有重要作用。IκB激酶β（IKKβ）是一种重要的激酶，通过启动多种细胞内信号级联反应对炎症刺激（如肿瘤坏死因子α（TNFα））作出反应，被认为是炎症介导的胰岛素抵抗发展中的关键因素。与预期相反，我们发现IKKβ介导的炎症是肝脏葡萄糖稳态的正调节因子。IKKβ磷酸化X-Box结合蛋白1（XBP 1 s）的剪接形式，并增加XBP 1 s的活性。我们已经使用了三种实验方法来增强肥胖小鼠肝脏中IKKβ的活性，并观察到增加的XBP 1 s活性，减少ER应激，以及胰岛素敏感性的显着改善，从而改善葡萄糖稳态。我们的研究结果揭示了IKKβ介导的肝脏炎症在葡萄糖稳态中的有益作用。肝脏中通过IKKβ的炎症信号传导有利于葡萄糖稳态，这与肥胖引起的炎症导致胰岛素抵抗的流行观点背道而驰
It is widely believed that inflammation associated with obesity has an important role in the development of type 2 diabetes. IκB kinase beta (IKKβ) is a crucial kinase that responds to inflammatory stimuli such as Tumor Necrosis Factor α (TNFα), by initiating a variety of intracellular signaling cascades, and is considered to be a key element in the inflammation-mediated development of insulin resistance. We show here, contrary to expectation, that IKKβ-mediated inflammation is a positive regulator of hepatic glucose homeostasis. IKKβ phosphorylates the spliced form of X-Box Binding Protein 1 (XBP1s) and increases the activity of XBP1s. We have used three experimental approaches to enhance the IKKβ activity in the liver of obese mice, and observed increased XBP1s activity, reduced ER stress, and a significant improvement in insulin sensitivity and consequently in glucose homeostasis. Our results reveal a beneficial role of IKKβ-mediated hepatic inflammation in glucose homeostasis. Inflammatory signaling via IKKβ in the liver is beneficial for glucose homeostasis, running counter to the prevailing view that inflammation caused by obesity leads to insulin resistance
登录
查看更多内容
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
影响因子：
64.5
作者：
Nakamura T;Furuhashi M;Li P;Cao H;Tuncman G;Sonenberg N;Gorgun CZ;Hotamisligil GS
通讯作者：
Hotamisligil GS
肿瘤坏死因子-α的脂肪表达--在与肥胖相关的胰岛素抵抗中的直接作用
影响因子：
56.9
作者：
HOTAMISLIGIL, GS;SHARGILL, NS;SPIEGELMAN, BM
通讯作者：
SPIEGELMAN, BM
影响因子：
15.9
作者：
Deng, Yingfeng;Wang, Zhao V.;Scherer, Philipp E.
通讯作者：
Scherer, Philipp E.
影响因子：
7.2
作者：
Gardner, Brooke M.;Pincus, David;Walter, Peter
通讯作者：
Walter, Peter