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Insulin: The Receptor and Signaling Pathways01:28

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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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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
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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 secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
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快照:胰岛素/IGF1信号传递

David K G Ma1, Christian Stolte2, James R Krycer3

  • 1Garvan Institute of Medical Research, Darlinghurst NSW 2010, Australia; School of Computer Science and Engineering, UNSW Sydney, NSW 2052, Australia.

Cell
|May 11, 2015
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概括

胰岛素/IGF1信号通路 (ISP) 对长期健康和寿命至关重要. 它的失调与2型糖尿病和衰老过程等疾病有关.

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科学领域:

  • 生物化学 生物化学
  • 分子生物学分子生物学
  • 遗传学 是一个遗传学.

背景情况:

  • 胰岛素/IGF1信号通路 (ISP) 是一种保存的细胞通路,调节基本的生物过程.
  • ISP中的干扰与衰老,代谢疾病 (如2型糖尿病) 和物种间寿命的确定有关.

研究的目的:

  • 阐明ISP在规范长期健康和寿命方面的作用.
  • 了解ISP扰动如何影响生物过程和疾病状态.
  • 探索ISP调节的机制,特别是蛋白质酸化网络.

主要方法:

  • 在不同的生物体中研究了胰岛素/IGF1信号通路 (ISP).
  • 分析了ISP干扰对寿命和健康寿命的影响.
  • 检查了生物过程的调节,包括能量储存,亡和转录.
  • 研究了蛋白质酸化网络在ISP信号传输中的作用.

主要成果:

  • ISP对于维持长期健康和影响寿命至关重要.
  • 特定的ISP变化与2型糖尿病和模型生物的寿命延长有关.
  • ISP控制了关键的细胞功能,如能量储存,细胞亡,转录和平衡.
  • 蛋白质酸化网络中的时间事件由ISP精确地重新连接.

结论:

  • 胰岛素/IGF1信号通路是健康和寿命的关键决定因素.
  • 了解ISP监管提供了关于衰老和代谢疾病的见解.
  • 精确控制蛋白质酸化动态是ISP功能的核心.