Knockdown of JNK rescues 3T3-L1 adipocytes from insulin resistance induced by mitochondrial dysfunction
Knockdown of JNK rescues 3T3-L1 adipocytes from insulin resistance induced by mitochondrial dysfunction
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DOI：
10.1016/j.bbrc.2008.11.121
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发表时间：
2009-01-23
影响因子：
3.1
通讯作者：
Draznin, Boris
中科院分区：
文献类型：
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作者：
Kiln, Toni;Leitner, J. Wayne;Draznin, Boris
线粒体功能障碍与胰岛素抵抗的病因有关，但其机制仍不清楚。在这项研究中，我们研究了氰化物对三氟甲氧基苯腙 (FCCP) 诱导的线粒体功能障碍是否会改变 3T3-L1 脂肪细胞的胰岛素敏感性，以及可能涉及哪些细胞信号分子。完全分化的3T3-L1脂肪细胞用10μM FCCP处理1小时，导致IRS-1的丝氨酸307磷酸化增加，胰岛素刺激的酪氨酸磷酸化减少，磷脂酰肌醇3激酶（PI 3激酶）的p85α亚基与IRS-1的关联，胰岛素刺激的PI 3激酶活性降低， H-3-2-脱氧葡萄糖 (2DOG) 摄取。 JNK1 的部分（46％）敲低可阻断 FCCP 诱导的 IRS-1 丝氨酸磷酸化，并恢复胰岛素刺激的 IRS-1 酪氨酸磷酸化，即 PI 3 激酶的 p85 α 亚基与 IRS-1 的关联。 PI 3-激酶的激活，以及2DOG摄取的刺激。因此，FCCP 诱导的线粒体功能障碍可能会导致胰岛素抵抗，而胰岛素抵抗可通过减少 JNK1 表达来改善。 (C) 2008 Elsevier Inc. 保留所有权利。
Mitochondrial dysfunction has been linked to etiology of insulin resistance, however the mechanism remains unknown. In this study we investigated whether mitochondrial dysfunction induced by cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) alters insulin sensitivity in 3T3-L1 adipocytes and which cellular signaling molecules might be involved. Fully differentiated 3T3-L1 adipocytes were treated with 10 mu M FCCP for 1 h, resulting in increased serine-307 phosphorylation of IRS-1 and decreased insulin-stimulated tyrosine phosphorylation, association of p85 alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase) with IRS-1, decreased insulin-stimulated PI 3-kinase activity and H-3-2-deoxyglucose (2DOG) uptake. A partial (46%) knockdown of JNK1 blocked FCCP-induced serine phosphorylation of IRS-1 and restored insulin-stimulated tyrosine phosphorylation of IRS-1, association of p85 alpha subunit of PI 3-kinase with IRS-1. activation of PI 3-kinase, and stimulation of 2DOG uptake. Thus, FCCP-induced mitochondrial dysfunction may cause insulin resistance that is ameliorated by reduction of JNK1 expression. (C) 2008 Elsevier Inc. All rights reserved.