It has been well established that hepatic insulin signaling is significantly affected by the antioxidative status of the liver. In this study, we first confirmed that skate skin collagen peptide (SSCP) administration has dose-dependent positive effects on the change in the glucose level as evidenced by oral glucose tolerance tests. Therefore, the beneficial effects of SSCP—showing antioxidative and anti-inflammatory activities—on insulin resistance were examined in high-fat diet (HFD)-fed mice. C57BL/6J mice orally received SSCP at doses of 100, 200, and 300 mg per kg bw per day along with a HFD for 8 weeks (n = 9 per group). Water was given to the HFD- or chow diet-only group as a vehicle. Compared with the HFD group, the final body weight was reduced in all the SSCP-treated groups in a dose-dependent manner. The hepatic protein expression levels of the phosphorylated insulin receptor substrate, phosphorylated phosphatidylinositol 3-kinase, and phosphorylated protein kinase B were increased in the SSCP-treated groups, which led to reduced plasma insulin and HOMA-IR levels (P < 0.05). The hepatic protein expression levels of nuclear factor erythroid 2-related factor 2-mediated antioxidant enzymes were increased in the SSCP-treated groups, whereas those of nuclear factor kappa B-regulated inflammatory enzymes and mediators were decreased (P < 0.05). These effects were dose-dependent. It is apparent that SSCP might enhance insulin sensitivity by increasing the antioxidative status and suppressing the inflammatory response in the liver.

中文翻译：

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滑冰（Raja kenojei）皮肤胶原蛋白肽通过减轻氧化应激和炎症改善胰岛素信号通路的作用

众所周知，肝脏的抗氧化状态会显着影响肝胰岛素信号传导。在这项研究中，我们首先证实滑冰皮肤胶原蛋白肽（SSCP）的给药对葡萄糖水平的变化具有剂量依赖性的积极作用，如口服葡萄糖耐量试验所证明的。因此，在高脂饮食（HFD）喂养的小鼠中检查了SSCP对胰岛素抵抗的有益作用-显示出抗氧化和抗炎活性。C57BL / 6J小鼠口服SSCP的剂量为每天100、200和300 mg / kg bw /天，并接受HFD治疗8周（n=每组9个）。将水作为一种媒介送给了仅食用高脂饮食或低脂饮食的人群。与HFD组相比，所有SSCP治疗组的最终体重均呈剂量依赖性降低。在SSCP治疗组中，磷酸化胰岛素受体底物，磷酸化磷脂酰肌醇3激酶和磷酸化蛋白激酶B的肝蛋白表达水平增加，导致血浆胰岛素和HOMA-IR水平降低（P <0.05）。在SSCP处理的组中，核因子红系2相关因子2介导的抗氧化酶的肝蛋白表达水平升高，而核因子κB调节的炎症酶和介质的肝蛋白表达水平降低（P<0.05）。这些作用是剂量依赖性的。显然，SSCP可以通过增加抗氧化状态并抑制肝脏的炎症反应来增强胰岛素敏感性。