INTRACELLULAR RECEPTORS AND METABOLIC CONTROL

细胞内受体和代谢控制

• 批准号: 3855985
• 负责人: D S MILLER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3855985
• 关键词: Xenopus; biological signal transduction; cell nucleus; cytoplasm; egg /ovum; genetic transcription; genetic translation; growth factor; insulin; insulin receptor; microinjections; peptide hormone; receptor; single cell analysis; vanadium; zinc

Complex organisms use chemical signals, e.g., polypeptide hormones and growth factors, to integrate and coordinate the function of specialized tissues. Information is transferred to target cells when hormones bind to specific surface receptors and cell structure and function can be profoundly affected. We have developed a powerful experimental system (consisting of a giant, insulin-sensitive cell (amphibian oocyte), paraffin oil-based cell microinjection and fractionation procedures and single cell microanalysis) to study how such information flows to intracellular metabolic control prints, i.e., to define postreceptor signalling mechanisms. Recent research has focused on the role of intracellular receptors in the mechanism of insulin action. We have shown that microinjected, intracellular insulin stimulates both transcription and translation in oocytes by acting directly at nuclear and cytoplasmic sites. Moreover, insulin action at internal sites also occurs when cells are exposed to extracellular hormone, since the insulin-stimulated component of protein synthesis is partially blocked when cells are first exposed to external hormone and then microinjected with anti-insulin antibody. Future plans include: 1) defining the mechanisms by which insulin gains access to the internal receptors, 2) determining the extent to which intracellular receptors are involved in the action of polypeptide hormones and growth factors in oocytes and in somatic cells, 3) assessing the role of disrupted intracellular signalling in pathological states, e.g., insulin resistance, and 4) investigating the mechanisms of action of insulin mimics, e.g., vanadate and zinc.

复杂的生物体使用化学信号，例如，多肽激素和 生长因子，整合和协调功能的专业化 组织中 当激素与靶细胞结合时， 特异性表面受体和细胞结构和功能， 深受影响。 我们开发了一个强大的实验系统 （由一个巨大的胰岛素敏感细胞（两栖类卵母细胞）组成， 基于油的细胞显微注射和分级程序以及单细胞 微分析）来研究这些信息如何流向细胞内 代谢控制指纹，即，来定义感受器后信号 机制等 最近的研究集中在细胞内的作用， 胰岛素作用机制中的受体。 我们已经证明 显微注射的细胞内胰岛素刺激转录和 通过直接作用于细胞核和细胞质位点在卵母细胞中进行翻译。 此外，胰岛素在内部位点的作用也发生在细胞被破坏时。 暴露于细胞外激素，因为胰岛素刺激的成分， 当细胞第一次暴露于 外源性激素，然后显微注射抗胰岛素抗体。 未来的计划包括：1）确定胰岛素增益的机制 进入内部受体，2）确定在何种程度上， 细胞内受体参与多肽激素的作用 和卵母细胞和体细胞中的生长因子，3）评估作用 在病理状态下，例如，胰岛素 抵抗，以及4）研究胰岛素的作用机制 模拟物，例如，钒酸盐和锌。