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Kursi Wufarikun Ziyabit 对 L6 大鼠骨骼肌细胞的降糖作用及其机制。

Anti-diabetic effect and mechanism of Kursi Wufarikun Ziyabit in L6 rat skeletal muscle cells.

机构信息

The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 40-1 Beijing Road, Urumqi, Xinjiang, 830011, China; University of the Chinese Academy of Sciences, No.19(A) Yuquan Road, Shijingshan District, Beijing, 100049, China.

The Key Laboratory of Plant Resources and Chemistry of Arid Zone, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 40-1 Beijing Road, Urumqi, Xinjiang, 830011, China; State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, 40-1 Beijing Road, Urumqi, Xinjiang, 830011, China.

出版信息

J Pharmacol Sci. 2018 Jun;137(2):212-219. doi: 10.1016/j.jphs.2018.06.011. Epub 2018 Jun 21.

Abstract

Kursi Wufarikun Ziyabit (KWZ) is a traditional prescription that used in folk tea drinking for its health care effect in treatment of type 2 diabetes mellitus (T2DM) in central Asia. However, the underlying mechanism of KWZ in T2DM has not been investigated extensively. This study designed to observe the effect of KWZ on glucose consumption and assess the molecular mechanism on associated proteins in insulin signaling and ER stress pathway in L6 rat skeletal muscle cells. The results showed that, KWZ exhibited proteins of PTP-1B and α-glycosidase inhibitory activity in vitro. No cytotoxicity of KWZ was found on L6 cell line. The best effect of glucose consumption of cells was shown at 6.25 μg/mL after KWZ treatment for 12 h. Expression of PTP-1B protein was inhibited by KWZ in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by KWZ. Moreover, the insulin-mediated induction of IRS-1 and GSK-3 were also activated by KWZ. Western blot results indicated that KWZ significantly improved the levels of ER stress proteins, which reduced the expression of GRP78, enhanced the expression of the PERK, eIF2α and XBP1s. The activation of PERK/eIF2α was likely consequence of GRP78 inhibition, and this might be beneficial for improving the stability of ER and alleviating insulin resistance. These results suggest that KWZ might be serving as the potential drug for the prevention and treatment of T2DM.

摘要

五茯热卡饮(KWZ)是一种传统方剂,在中亚民间饮茶中被用于治疗 2 型糖尿病(T2DM),具有保健作用。然而,KWZ 治疗 T2DM 的潜在机制尚未得到广泛研究。本研究旨在观察 KWZ 对葡萄糖消耗的影响,并评估其对胰岛素信号和内质网应激途径相关蛋白的分子机制。结果表明,KWZ 在体外表现出 PTP-1B 和α-糖苷酶抑制活性。KWZ 对 L6 细胞系无细胞毒性。KWZ 处理 12 小时后,细胞葡萄糖消耗的最佳效果出现在 6.25μg/mL。KWZ 抑制 L6 成肌细胞中 PTP-1B 蛋白的表达。发现 KWZ 激活了 PI3K 依赖性 Akt 磷酸化。此外,KWZ 还激活了胰岛素介导的 IRS-1 和 GSK-3 的诱导。Western blot 结果表明,KWZ 显著改善了内质网应激蛋白的水平,降低了 GRP78 的表达,增强了 PERK、eIF2α 和 XBP1s 的表达。PERK/eIF2α 的激活可能是由于 GRP78 的抑制,这可能有利于改善 ER 的稳定性并减轻胰岛素抵抗。这些结果表明,KWZ 可能是预防和治疗 T2DM 的潜在药物。

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