Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine
Insulin resistance in vitamin D-deficient mice is alleviated by n-acetylcysteine
复制标题
n-乙酰半胱氨酸可减轻维生素 D 缺乏小鼠的胰岛素抵抗
DOI：
10.18632/oncotarget.18793
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发表时间：
2017-09-08
期刊：
影响因子：
--
通讯作者：
Tao, Sha
中科院分区：
文献类型：
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作者：
Cui, Zhao-Hui;Yuan, Qi;Tao, Sha
维生素D缺乏会导致胰岛素抵抗。在当前的研究中，生成了维生素 D3 1 α-羟化酶 [“1 α(OH)ase”] 敲除小鼠来模拟体内维生素 D 缺乏症。与野生型小鼠相比，基因敲除小鼠的肝组织显示出胰岛素信号受损、葡萄糖转运蛋白4表达减少以及活性氧产生增加。同时，敲除小鼠肝脏中p53-p21激活、细胞凋亡强度和促炎细胞因子（IL-6、IL-1和MIP-1α）水平显着增加。值得注意的是，通过补充抗氧化剂 n-乙酰半胱氨酸（NAC），基因敲除小鼠的这种影响在很大程度上减弱。值得注意的是，经过 NAC 治疗后，基因敲除小鼠的胰岛素抵抗和代谢异常得到了很大程度的缓解。因此，NAC 抑制氧化应激可减轻维生素 D 缺乏小鼠的胰岛素抵抗。氧化应激可能是维生素 D 缺乏导致胰岛素抵抗的主要原因。
Vitamin D deficiency will lead to insulin resistance. In the current study, vitamin D3 1 alpha-Hydroxylase ["1 alpha(OH)ase"] knockout mice were generated to mimic vitamin D deficiency in vivo. As compared to the wild-type mice, the liver tissues of the knockout mice showed impaired insulin signaling, decreased glucose transporter 4 expression and increased reactive oxygen species production. Meanwhile, p53-p21 activation, apoptosis intensity and pro-inflammatory cytokines (IL-6, IL-1 and MIP-1 alpha) level were significantly increased in the knockout mice livers. Significantly, such effects in the knockout mice were largely attenuated by supplement with anti-oxidant n-acetylcysteine (NAC). Remarkably, insulin resistance and metabolic abnormalities in the knockout mice were largely alleviated after treatment of NAC. Therefore, inhibition of oxidative stress by NAC alleviated insulin resistance in vitamin D-deficient mice. Oxidative stress could be the primary cause of insulin resistance by vitamin D deficiency.