11β-Hydroxysteroid Dehydrogenase Type 1(11β-HSD1) mediates insulin resistance through JNK activation in adipocytes.
11β-Hydroxysteroid Dehydrogenase Type 1(11β-HSD1) mediates insulin resistance through JNK activation in adipocytes.
复制标题
11β-羟基类固醇脱氢酶 1 型 (11β-HSD1) 通过脂肪细胞中的 JNK 激活介导胰岛素抵抗
DOI：
10.1038/srep37160
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发表时间：
2016-11-14
影响因子：
4.6
通讯作者：
Zheng C
中科院分区：
文献类型：
--
作者：
Peng K;Pan Y;Li J;Khan Z;Fan M;Yin H;Tong C;Zhao Y;Liang G;Zheng C
糖皮质激素被用于治疗许多人类疾病，但通常会导致胰岛素抵抗和代谢综合征。11β-羟基类固醇脱氢酶1(11β-HSD1)是催化细胞内皮质醇转化为生理活性皮质醇的关键酶。尽管已知11β-HSD1和活性糖皮质激素在导致胰岛素抵抗中的作用，但诱导胰岛素抵抗的分子机制仍然不清楚。这项研究的目的是在高脂饮食(HFD)的实验模型中确定这些机制。用11种β-hsd1抑制剂和一种jnk抑制剂治疗高血压性肝病小鼠。然后，我们用强的松(一种合成的糖皮质激素)处理3T3-L1来源的脂肪细胞和11个β-hsd1过表达的细胞来研究胰岛素抵抗。我们的结果表明，11β-hsd1和Jnk抑制减轻了肾衰小鼠的胰岛素抵抗。强的松刺激或11JNKHSD1的过表达也可引起脂肪细胞β的激活。抑制11β-HSD1可阻断肾衰小鼠脂肪组织和培养脂肪细胞中JNK1的激活。此外，泼尼松显著损害胰岛素信号转导通路，这些作用可被11β-hsd1和jnk抑制所逆转。我们的研究表明，糖皮质激素诱导的胰岛素抵抗依赖于11JNK-HSD1，导致脂肪细胞中β信号的关键激活。
Glucocorticoids are used to treat a number of human diseases but often lead to insulin resistance and metabolic syndrome. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a key enzyme that catalyzes the intracellular conversion of cortisone to physiologically active cortisol. Despite the known role of 11β-HSD1 and active glucocorticoid in causing insulin resistance, the molecular mechanisms by which insulin resistance is induced remain elusive. The aim of this study is to identify these mechanisms in high fat diet (HFD) experimental models. Mice on a HFD were treated with 11β-HSD1 inhibitor as well as a JNK inhibitor. We then treated 3T3-L1-derived adipocytes with prednisone, a synthetic glucocorticoid, and cells with 11β-HSD1 overexpression to study insulin resistance. Our results show that 11β-HSD1 and JNK inhibition mitigated insulin resistance in HFD mice. Prednisone stimulation or overexpression of 11β-HSD1 also caused JNK activation in cultured adipocytes. Inhibition of 11β-HSD1 blocked the activation of JNK in adipose tissue of HFD mice as well as in cultured adipocytes. Furthermore, prednisone significantly impaired the insulin signaling pathway, and these effects were reversed by 11β-HSD1 and JNK inhibition. Our study demonstrates that glucocorticoid-induced insulin resistance was dependent on 11β-HSD1, resulting in the critical activation of JNK signaling in adipocytes.
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通过蛋白激酶C-β同工型在内皮中诱导血管胰岛素抵抗和内皮蛋白-1表达以及动脉粥样硬化的加速。
影响因子：
20.1
作者：
Li Q;Park K;Li C;Rask-Madsen C;Mima A;Qi W;Mizutani K;Huang P;King GL
通讯作者：
King GL
影响因子：
4.4
作者：
Cote-Velez, Antonieta;Perez-Martinez, Leonor;Joseph-Bravo, Patricia
通讯作者：
Joseph-Bravo, Patricia
影响因子：
4.8
作者：
Harno, Erika;Cottrell, Elizabeth C.;White, Anne
通讯作者：
White, Anne
影响因子：
4.8
作者：
Fuerst, Robert;Zahler, Stefan;Vollmar, Angelika M.
通讯作者：
Vollmar, Angelika M.
影响因子：
--
作者：
Gao, ZG;Zhang, XY;Ye, JP
通讯作者：
Ye, JP