Oxidant stress and skeletal muscle glucose transport: Roles of insulin signaling and p38 MAPK
Oxidant stress and skeletal muscle glucose transport: Roles of insulin signaling and p38 MAPK
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DOI：
10.1016/j.freeradbiomed.2006.05.031
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发表时间：
2006-09-01
影响因子：
7.4
通讯作者：
Henriksen, Erik J.
中科院分区：
文献类型：
--
作者：
Kim, John S.;Saengsirisuwan, Vitoon;Henriksen, Erik J.
氧化应激可影响多种细胞系中葡萄糖转运活性的调节。在目前的研究中，我们评估了氧化剂应激对完整哺乳动物骨骼肌制剂中葡萄糖运输系统的直接影响。将胰岛素敏感型瘦肉型Zucker大鼠的IIb型(上丘肌)和I型(比目鱼肌)在8 mM葡萄糖中孵育2b，不加或不加100mU/ml葡萄糖氧化酶，产生氧化剂过氧化氢(H202)(60~90mU/mM)。然后评估葡萄糖转运、糖原合成酶活性和代谢信号因子。过氧化氢显著(p<；0.05)激活两种肌肉的基础葡萄糖转运和糖原合成酶活性，并增加胰岛素受体酪氨酸磷酸化、与磷脂酰肌醇-3‘激酶P85亚单位相关的胰岛素受体底物-1和Akt的Ser(473)磷酸化。氧化应激诱导的葡萄糖转运可被PI3-激酶抑制剂Wortmannin阻止。氧化应激还显著增加了p38丝裂原活化蛋白激酶(P38MAPK)和5‘-AMP依赖的蛋白激酶的磷酸化。有趣的是，使用A304000选择性地抑制p38MAPK大大减少了氧化应激诱导的葡萄糖运输的激活。这些结果支持氧化应激在哺乳动物骨骼肌葡萄糖运输系统激活中的直接作用，并表明这一过程涉及PI3依赖的信号通路和p38MAPK的激活以及可能的相互作用。(C)2006 Elsevier Inc.保留所有权利。
Oxidative stress can impact the regulation of glucose transport activity in a variety of cell lines. In the present study, we assessed the direct effects of an oxidant stress on the glucose transport system in intact mammalian skeletal muscle preparations. Type IIb (epitrochlearis) and type I (soleus) muscles from insulin-sensitive lean Zucker rats were incubated in 8 mM glucose for 2 b in the absence or presence of 100 mU/ml glucose oxidase to produce the oxidant hydrogen peroxide (H2O2) (60-90 mu M). Glucose transport, glycogen synthase activity, and metabolic signaling factors were then assessed. H2O2 significantly (p < 0.05) activated basal glucose transport and glycogen synthase activities and increased insulin receptor tyrosine phosphorylation, insulin receptor substrate-1 associated with the p85 subunit of phosphatidylinositol-3' kinase (PI3-kinase), and Ser(473) phosphorylation of Akt in both muscle types. This induction of glucose transport by the oxidant stress was prevented by the PI3-kinase inhibitor wortmannin. The oxidant stress also significantly increased phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) and 5'-AMP-dependent protein kinase. Interestingly, selective inhibition of p38 MAPK using A304000 substantially reduced the activation of glucose transport induced by the oxidant stress. These results support a direct role for oxidative stress in the activation of the glucose transport system in mammalian skeletal muscle and indicate that this process involves engagement of and possible interactions between the PI3-kinase-dependent signaling pathway and activation of p38 MAPK. (c) 2006 Elsevier Inc. All rights reserved.