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相关概念视频

Cell Specific Gene Expression01:58

Cell Specific Gene Expression

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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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Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

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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.
Insulin and C-peptide are...
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Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

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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.
In addition to accelerating glucose uptake and utilization, insulin has...
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Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

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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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PI3K/mTOR/AKT Signaling Pathway01:22

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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 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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A High-content In Vitro Pancreatic Islet β-cell Replication Discovery Platform
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I-BET151调节葡萄酶基因表达和β细胞功能,部分通过FOXO1表达的变化.

Qing Wei Calvin Ho1, James A Miller1, Divya Gunaseelan1

  • 1Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore, Republic of Singapore.

Diabetologia
|September 26, 2025
PubMed
概括

抑制BET可能会损害胰腺β细胞功能. 这项研究发现,I-BET151降低了小鼠的葡萄糖调节和胰岛素分泌,影响了关键的β细胞基因. 建议在使用BET抑制剂治疗时谨慎使用.

关键词:
BET 蛋白抑制剂的使用贝塔细胞 贝塔细胞 贝塔细胞表观遗传调节器 表观遗传调节器这就是FOXO1的意义.GCK GCK 在线观看这就是HNF4a.在I-BET151中.这里是INS-1E.莫迪 (MODY) 的意思是说.胰腺小岛是一个小岛.

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科学领域:

  • 表观遗传学和分子生物学
  • 内分泌学和新陈代谢
  • 癌症生物学 癌症生物学

背景情况:

  • 原体和外终端 (BET) 蛋白质是表观遗传阅读器,调节基因转录.
  • BET蛋白与癌症和1型糖尿病等疾病有关.
  • 对BET抑制剂对宿主细胞的潜在非向作用需要进行研究.

研究的目的:

  • 研究BET抑制对胰腺β细胞功能的二次影响.
  • 确定BET抑制剂I-BET151对葡萄糖恒温和胰岛素分泌的影响.
  • 确定BET抑制对β细胞的影响背后的分子机制.

主要方法:

  • 使用BET抑制剂I-BET151.1.进行体外,体外和体内研究.
  • 在小鼠中进行葡萄糖耐受性测试 (GTT) 和胰岛素耐受性测试 (ITT).
  • 葡萄糖刺激胰岛素分泌量测定和动物和人类小岛的转录基因分析.

主要成果:

  • 在健康和糖尿病小鼠中,I-BET151的使用增加了葡萄糖外流,并减少了胰岛素反应.
  • I-BET151显著降低了必不可少的β细胞功能基因 (例如,Hnf4α,Gck,Hnf1α,Glut2) 的表达.
  • 转录组分析显示PI3K-Akt通路的下调,FOXO1调节有部分拯救作用.

结论:

  • 抑制BET可能对胰腺β细胞功能产生有害影响.
  • 高度的BET抑制剂可能会对葡萄糖调节和胰岛素分泌产生负面影响.
  • 由于对β细胞的潜在不良影响,BET抑制剂的治疗用途需要谨慎使用.