Peptide IPPKKNQDKTE ameliorates insulin resistance in HepG2 cells via blocking ROS-mediated MAPK signaling
Peptide IPPKKNQDKTE ameliorates insulin resistance in HepG2 cells via blocking ROS-mediated MAPK signaling
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肽 IPPKKNQDKTE 通过阻断 ROS 介导的 MAPK 信号传导改善 HepG2 细胞的胰岛素抵抗
DOI：
10.1016/j.jff.2017.02.005
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发表时间：
2017-04
影响因子：
5.6
通讯作者：
Mao Xue-ying
中科院分区：
文献类型：
--
作者：
Song Jia-jia;Wang Qian;Du Min;Chen Bin;Mao Xue-ying
活性氧在胰岛素抵抗中起重要作用。本研究检测了肽IPPKKNQDKTE对肝胰岛素抵抗的改善作用是否通过ROS清除介导。结果表明，IPPKKNQDKTE可抑制高糖诱导的胰岛素抵抗HepG 2细胞MAPK信号通路的激活，这可能与IPPKKNQDKTE提高细胞葡萄糖摄取和胰岛素受体底物-1（IRS-1）Ser 636/639和Ser 307磷酸化水平有关。IPPKKNQDKTE剂量依赖性地减少高糖诱导的ROS产生，这参与了IPPKKNQDKTE对高糖诱导的胰岛素抵抗HepG 2细胞中MAPK信号的抑制。此外，IPPKKNQDKTE增加Nrf 2核转位和诱导HO-1表达。HO-1抑制剂可部分逆转IPPKKNQDKTE对高糖诱导的ROS产生的抑制作用。总之，IPPKKNQDKTE通过激活Nrf 2/HO-1减少高糖诱导的ROS产生和MAPK激活，这有助于增加胰岛素抵抗HepG 2细胞的葡萄糖摄取和降低IRS-1的Ser磷酸化水平。这些结果表明，IPPKKNQDKTE在肝脏胰岛素抵抗的管理中起着潜在的作用。
Reactive oxygen species (ROS) has been found to play an important role in insulin resistance. Whether the improvement effects of the peptide IPPKKNQDKTE on hepatic insulin resistance were mediated by ROS elimination was examined in this study. Results showed that the high glucose-induced MAPK signaling activation was inhibited by IPPKKNQDKTE in insulin-resistant HepG2 cells, which contributed to the improvement of IPPKKNQDKTE on cellular glucose uptake and the phosphorylation levels of insulin receptor substrate-1 (IRS-1) Ser636/639 and Ser307. IPPKKNQDKTE dose-dependently reduced high glucose-induced ROS production, which involved in suppression of IPPKKNQDKTE on MAPK signaling in high glucose-induced insulin-resistant HepG2 cells. Moreover, IPPKKNQDKTE increased Nrf2 nucleus translocation and induced HO-1 expression. HO-1 inhibitor partly reversed IPPKKNQDKTE-mediated suppression on high glucose-induced ROS production. Taken together, IPPKKNQDKTE reduced high glucose-induced ROS production and MAPK activation by the activation of Nrf2/HO-1, which contributed to increase the glucose uptake and decrease the Ser phosphorylation levels of IRS-1 in insulin-resistant HepG2 cells. These results indicated that IPPKKNQDKTE plays a potential role in the management of hepatic insulin resistance.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
13.6
作者：
Schram, Miranda T.;Sep, Simone J. S.;Stehouwer, Coen D. A.
通讯作者：
Stehouwer, Coen D. A.
影响因子：
3
作者：
Zhu Ming;Yuchen Jia;Yali Yan;Guangchang Pang;Qingsen Chen
通讯作者：
Zhu Ming;Yuchen Jia;Yali Yan;Guangchang Pang;Qingsen Chen
影响因子：
16
作者：
Michael, MD;Kulkarni, RN;Kahn, CR
通讯作者：
Kahn, CR
DOI：
10.1073/pnas.1311176110
发表时间：
2013-07-30
影响因子：
11.1
作者：
Galbo, Thomas;Perry, Rachel J.;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.