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首页> 外文学位 >Novel protein phosphatase 2A complexes in skeletal muscle from obese insulin resistant human participants.
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Novel protein phosphatase 2A complexes in skeletal muscle from obese insulin resistant human participants.

机译：肥胖胰岛素抵抗性人类参与者骨骼肌中的新型蛋白磷酸酶2A复合物。

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摘要

Type 2 Diabetes is a metabolic disorder associated with insulin resistance and consequent high blood glucose levels. Maximum glucose disposal takes place in skeletal muscle and studying skeletal muscle insulin resistance is crucial. Protein Phosphatase 2A (PP2A) is one of the major serine/threonine phosphatases belonging to PhosphoProteinPhosphatase (PPP) family. It constitutes about 80% of all serine/threonine phosphatases. It is regulated by numerous regulatory subunits as well as other substrate molecules and post translational modifications. This alters their localization, activity and also its target molecules. Many evidences show the effect of insulin on PP2Ac and its abnormal regulation in conditions of glucolipotoxicity. Thus, studying PP2Ac interaction partners in respect to type 2 diabetes will give insight into its role in insulin resistance.;Here, we studied interaction partners of PP2Ac in obese insulin resistant human subjects. Two skeletal muscle biopsies, basal and insulin stimulated are obtained from each individual using hyperinsulenemic euglycemic clamp technique. Using ESI-HPLC-MS/MS, we identified 186 interaction partners. Out of which 14 partners were previously identified by other groups which leaves 172 novel partners. This is the largest PP2Ac interaction network found till date. We also identified 17 insulin responsive PP2Ac partners. Several important PP2Ac interaction partners molecules were identified, for the 1st time, in skeletal muscle from humans. Among them, some are known to affect PP2Ac activity and others are significantly associated with insulin signaling. Further validation of these partners will help with a better understanding of the role and regulation of PP2Ac in terms of insulin resistance in obese individuals.
机译：2型糖尿病是一种与胰岛素抵抗和随之而来的高血糖水平相关的代谢异常。最大的葡萄糖处置发生在骨骼肌中，研究骨骼肌的胰岛素抵抗至关重要。蛋白磷酸酶2A（PP2A）是属于磷酸蛋白磷酸酶（PPP）家族的主要丝氨酸/苏氨酸磷酸酶之一。它约占所有丝氨酸/苏氨酸磷酸酶的80％。它受众多调控亚基以及其他底物分子和翻译后修饰的调控。这改变了它们的定位，活性以及它的靶分子。许多证据表明胰岛素在糖脂毒性条件下对PP2Ac的作用及其异常调节。因此，研究与2型糖尿病有关的PP2Ac相互作用伴侣将有助于深入了解其在胰岛素抵抗中的作用。在这里，我们研究了在肥胖的胰岛素抵抗人类受试者中PP2Ac的相互作用伴侣。使用高胰岛素血症的正常血糖钳夹技术从每个人获得两个骨骼肌活检，分别是基础刺激和胰岛素刺激。使用ESI-HPLC-MS / MS，我们确定了186个相互作用伙伴。在其他小组之前已确定了14个合作伙伴，剩下172个新的合作伙伴。这是迄今为止发现的最大的PP2Ac交互网络。我们还确定了17个胰岛素反应性PP2Ac伙伴。首次在人的骨骼肌中鉴定出几个重要的PP2Ac相互作用伴侣分子。其中，一些已知会影响PP2Ac活性，而另一些则与胰岛素信号显着相关。这些伙伴的进一步验证将有助于更好地了解肥胖个体中PP2Ac在胰岛素抵抗方面的作用和调节。

著录项

  • 作者

    Damacharla, Divyasri.;

  • 作者单位

    Wayne State University.;

  • 授予单位 Wayne State University.;
  • 学科 Pharmaceutical sciences.;Pharmacology.
  • 学位 M.S.
  • 年度 2015
  • 页码 67 p.
  • 总页数 67
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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