• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Metabolic role of thioredoxin-interacting protein in facilitating the fasting response.
【24h】

Metabolic role of thioredoxin-interacting protein in facilitating the fasting response.

机译：硫氧还蛋白相互作用蛋白在促进空腹反应中的代谢作用。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Thioredoxin-interacting protein (Txnip) is a ubiquitously expressed protein whose well established function is to bind to thioredoxin, effectively inhibiting its ability to facilitate redox-mediated functions. Txnip has been characterized as a potent tumor suppressor and (through its association with thioredoxin) is involved in various cellular homeostatic functions that regulate cell growth, proliferation, and apoptosis. Recently, Txnip has emerged as an important player in metabolism.;Here, we demonstrate that Txnip is essential for integrating signals that allow for an appropriate metabolic response to survive a fasting challenge. Using a mouse model harboring genetic disruption of the Txnip gene, we attempted to elucidate the role of Txnip in facilitating the fasting response where the body normally elicits a set of metabolic reactions to maintain energy homeostasis necessary for survival. We establish that loss of Txnip alone is sufficient to induce fasting hypoglycemia, hyperketonemia and hypertriglyceridemia. Furthermore, we show that Txnip ablation leads to attenuated mitochondrial oxidative phosphorylation of all major fuel substrate types (glucose, ketone bodies, and fatty acids) and enhances the propensity to utilize glucose in muscle tissues. Moreover, we establish that Txnip exerts its metabolic role in the fasting response in great part through the heart and skeletal muscles, as the phenotype of global Txnip knockout mice is closely recapitulated in the heart and skeletal muscle-specific knockout mice.;Upon concentrating our efforts to understand the function of Txnip in the heart and skeletal muscle of fasting Txnip -/- mice, we observed hypoactivation of AMPK in the more oxidative muscle tissues (heart and soleus muscles) relative to their controls. We found that this phenomenon is a consequence of a low AMP:ATP ratio (high energy state) and is associated with increased muscle glycogen content. In this dissertation we demonstrate that Txnip is an essential player for facilitating the glucose-fatty acid cycle, which is an essential part of the fasting response. Because of the critical and influential role it plays in cellular energetics and house keeping functions, Txnip may be a potentially good target for therapeutic research into treating many of the metabolic maladies man faces today that include heart disease, cancer, and diabetes.
机译：硫氧还蛋白相互作用蛋白（Txnip）是一种普遍表达的蛋白，其功能完善的功能是与硫氧还蛋白结合，有效抑制其促进氧化还原介导的功能的能力。 Txnip被认为是有效的肿瘤抑制物，并且（通过与硫氧还蛋白的结合）参与调节细胞生长，增殖和凋亡的各种细胞稳态功能。最近，Txnip已成为新陈代谢的重要参与者。在这里，我们证明Txnip对于整合信号是必不可少的，这些信号允许适当的代谢反应以抵抗空腹挑战。我们使用具有Txnip基因遗传破坏的小鼠模型，试图阐明Txnip在促进空腹反应中的作用，在该空腹反应中，人体通常会引发一系列代谢反应，以维持生存所必需的能量稳态。我们建立了单独的Txnip丧失足以诱发空腹低血糖，高酮血症和高甘油三酸酯血症。此外，我们显示Txnip消融导致所有主要燃料底物类型（葡萄糖，酮体和脂肪酸）的线粒体氧化磷酸化减弱，并增强了在肌肉组织中利用葡萄糖的倾向。此外，我们确定Txnip在很大程度上通过心脏和骨骼肌在空腹反应中发挥其代谢作用，因为全球性Txnip基因敲除小鼠的表型在心脏和骨骼肌特异性基因敲除小鼠中具有很强的概括性。为了了解Txnip在禁食Txnip-/-小鼠的心脏和骨骼肌中的功能，我们观察到相对于其对照，在氧化性更强的肌肉组织（心脏和比目鱼肌）中AMPK的激活不足。我们发现这种现象是由于AMP：ATP比例低（高能态）的结果，并且与肌肉糖原含量增加有关。在本文中，我们证明了Txnip是促进葡萄糖-脂肪酸循环的重要参与者，而葡萄糖-脂肪酸循环是禁食反应的重要组成部分。由于Txnip在细胞能量学和家务功能中起着至关重要的作用，因此Txnip可能成为治疗研究人类当今面临的许多代谢性疾病（包括心脏病，癌症和糖尿病）的治疗研究的潜在目标。

著录项

  • 作者

    Andres, Allen Mariano.;

  • 作者单位

    University of California, San Diego and San Diego State University.;

  • 授予单位 University of California, San Diego and San Diego State University.;
  • 学科 Biology Molecular.;Biology Physiology.;Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 136 p.
  • 总页数 136
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 人口学;
  • 关键词

  • 入库时间 2022-08-17 11:38:19

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号