Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes
Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes
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DOI：
10.1016/j.febslet.2015.11.029
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发表时间：
2015-12
期刊：
影响因子：
3.5
通讯作者：
Xiaolin Ji;Lili Yao;Meihong Wang;Xiaoyu Liu;S. Peng;Kaixuan Li;Muchen Xu;Ningmei Shen;Lan Luo;Cheng Sun
中科院分区：
文献类型：
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作者：
Xiaolin Ji;Lili Yao;Meihong Wang;Xiaoyu Liu;S. Peng;Kaixuan Li;Muchen Xu;Ningmei Shen;Lan Luo;Cheng Sun
据报道，胱抑素C（Cys C）与代谢紊乱如肥胖和糖尿病密切相关。然而，Cys C是否在这些疾病中发挥作用仍然是未知的。我们的结果表明，胰岛素信号转导在很大程度上受到Cys C在肝细胞中的损害。然而，在肌管中，胰岛素信号转导不受影响。Cys C可诱导肝细胞内质网应激（endoplasmic reticulum stress，ER stress），而对肌管无此作用。4-苯基丁酸（4-PBA）缓解ER应激恢复Cys C处理的肝细胞中受损的胰岛素信号转导。这些结果为Cys C通过诱导内质网应激损伤肝细胞胰岛素信号转导提供了直接证据。
It has been reported that cystatin c (Cys C) closely correlates with metabolic disorders such as obesity and diabetes. However, it is still unknown whether Cys C plays a role for these disorders. Our results showed that the insulin signal transduction was largely impaired by Cys C in hepatocytes. In myotubes, however, the insulin signal transduction was not affected. Following experiments revealed that Cys C could induce endoplasmic reticulum stress (ER stress) in hepatocytes, whereas Cys C had no such an effect in myotubes. The alleviation of ER stress by 4-Phenyl butyric acid (4-PBA) restored the impaired insulin signal transduction in Cys C-treated hepatocytes. These results provided direct evidence that, by inducing ER stress, Cys C impairs insulin signal transduction in hepatocytes.