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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
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The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
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Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
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抗胰岛素的心脏表现出线粒体生物的反应驱动的氧酶增殖器激活受体-alpha/PGC-1alpha基因调节通路.

Jennifer G Duncan1, Juliet L Fong, Denis M Medeiros

  • 1Center for Cardiovascular Research, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, MO 63110, USA.

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|January 31, 2007
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概括

线粒体生物发生在胰岛素抵抗的早期被激活,而糖尿病则是先前的. 这一过程涉及酶增殖器激活受体-α (PPARalpha) 激活PPARgamma联合激活器-1alpha (PGC-1alpha) 基因表达,导致心脏功能障碍.

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科学领域:

  • 心血管生物学 心血管生物学
  • 代谢性疾病 代谢性疾病
  • 线粒体生物学 线粒体生物学

背景情况:

  • 肥胖和糖尿病导致心血管疾病死亡率.
  • 在糖尿病动物模型中观察到心脏线粒体功能的改变.
  • 这项研究调查了早期胰岛素抵抗期间的线粒体调节.

研究的目的:

  • 测试线粒体功能调节事件是否在糖尿病前,胰岛素耐药阶段被激活.
  • 阐明在胰岛素耐药性期间心脏线粒体生物生成中氧酶增殖器激活受体-α (PPARalpha) 的作用.

主要方法:

  • 使用了抗胰岛素解蛋白-双毒素A (UCP-DTA) 转基因小鼠和PPARalpha-null小鼠.
  • 进行了形态测量分析,线粒体DNA含量测量和基因表达分析.
  • 研究了PPARalpha和PPARgamma联合激活剂-1alpha (PGC-1alpha) 在线粒体生物生成中的作用.

主要成果:

  • 在胰岛素抵抗性UCP-DTA小鼠中增加心肌细胞线粒体体积密度和基因表达.
  • PPARalpha激活对于线粒体生物发生和PGC-1alpha诱导在抗胰岛素的心脏中至关重要.
  • 特定于心脏的PPARalpha过度表达诱导了线粒体生物发生的特征.

结论:

  • 线粒体生物发生在糖尿病心脏功能障碍发育的早期.
  • 一个涉及PPARalpha激活PGC-1alpha的调节电路驱动线粒体生物发生.
  • 这一途径在糖尿病前,胰岛素耐药阶段被激活.