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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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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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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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When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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一个逐步激活胰岛素受体的模型.

Na-Oh Yunn1, Junhong Kim2, Sung Ho Ryu2

  • 1Postech Biotech Center, Pohang University of Science and Technology (POSTECH), Pohang, 37673, Republic of Korea. beback13@postech.ac.kr.

Experimental & molecular medicine
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概括

胰岛素受体 (IR) 的激活是复杂的. 本综述探讨了带有配体和体的IR结构,提出了一种序列激活模型,并讨论了针对性治疗的偏向激动剂.

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科学领域:

  • 生物化学 生物化学
  • 结构生物学 结构生物学
  • 药理学 药理学是指药理学的学科.

背景情况:

  • 胰岛素受体 (IR) 的激活启动关键的代谢和菌原体信号通路.
  • 虽然已知非活跃和完全活跃的IR结构,但早期激活步骤仍然不清楚.
  • 了解IR激活是代谢疾病研究的关键.

研究的目的:

  • 阐明胰岛素受体早期激活机制.
  • 审查IR的结构和功能数据,并与各种连接体进行复合.
  • 提出一个连续的IR激活的模型,并讨论偏见的激动剂.

主要方法:

  • 部分激活的红外吸收体复合物的结构分析.
  • 功能分析 IR 复合体与多种连接体.
  • 审查现有的结构和功能数据.

主要成果:

  • 部分激活的IR结构为初始形状变化提供了洞察力.
  • 提出了胰岛素受体的顺序激活模型.
  • 讨论了选择性激活代谢途径的偏差激动剂.

结论:

  • 通过结构研究,可以更好地了解胰岛素受体的早期激活机制.
  • 一个序列模型解释了各种连接体的IR激活.
  • 选择性激动剂在代谢疾病中具有针对性治疗策略的潜力.