Sensing the insulin signaling pathway with an antibody array.
Sensing the insulin signaling pathway with an antibody array.
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DOI：
10.1002/prca.200900020
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发表时间：
2009-12
影响因子：
2
通讯作者：
Wang, Lili
中科院分区：
文献类型：
--
作者：
He, Hua-Jun;Zong, Yaping;Bernier, Michel;Wang, Lili
关键词：
胰岛素抵抗和2型糖尿病的发展是由多种因素决定的，包括胰岛素信号通路的缺陷。胰岛素抵抗的介质通过激活各种蛋白激酶C （PKC）异构体、i - κ b激酶β (IKKβ)和/或C - jun n末端激酶（JNK），以及随后通过胰岛素受体底物1 （IRS1）和Akt抑制近端胰岛素信号通路而起作用。由于分子事件的复杂性，这些机制在很大程度上仍未得到解决。在这项研究中，我们利用磷酸特异性抗体阵列平台评估了胰岛素代谢和有丝分裂信号通路中涉及的多个已知关键信号生物分子的表达和激活状态。通过多重头阵列实验和传统的western blot分析验证了抗体的排列结果，证实了佛波酯对胰岛素信号通路激活的抑制作用。有趣的是，磷酸酯介导的PKC信号反应的增加与脂质磷酸酶PTEN和27 kDa热休克蛋白的激活有关。因此，这种胰岛素信号抗体阵列为研究胰岛素抵抗机制提供了一种强大而有效的方法，并可能有助于开发创新的2型糖尿病治疗药物。
The development of insulin resistance and type 2 diabetes is determined by various factors, including defects within the insulin signaling pathway. Mediators of insulin resistance operate through activation of various protein kinase C (PKC) isoforms, IκB kinase β (IKKβ) and/or c-Jun N-terminal kinase (JNK), and subsequent inhibition of the proximal insulin signaling pathway via the insulin receptor substrate 1 (IRS1) and Akt. These mechanisms are still largely unresolved because of the complexity of the molecular events. In this study, an expression and activation state profiling of multiple known key signaling biomolecules involved in insulin metabolic and mitogenic signaling pathways was evaluated using a phosphospecific antibody array platform. The results of the arrayed antibodies were verified by the multiplexed bead array assay and conventional western blot analysis, and confirmed the well-known inhibitory effects of phorbol esters on insulin signaling pathway activation. Of interest, the increase in PKC signaling responses with phorbol esters was associated with activation of the lipid phosphatase PTEN and a 27 kDa heat shock protein. Thus, this insulin signaling antibody array provides a powerful and effective way to investigate the mechanism of insulin resistance and likely assist the development of innovative therapeutic drugs for type 2 diabetes.
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影响因子：
82.9
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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作者：
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DOI：
10.1073/pnas.0711713105
发表时间：
2008-02-19
影响因子：
11.1
作者：
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通讯作者：
Mann, Matthias