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After cellular or tissue damage, the resident stem cells present in the human body can locally repair and regenerate the damaged tissue or organ. However, even though some tissues do not have stem cells, they can repair and regenerate with the help of pre-existing cells. For example, beta cells of the pancreas and hepatocytes of the liver can divide to renew and regenerate the tissue. Here, both cell division and cell death are well regulated by homeostasis.
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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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使用干细胞衍生的α细胞建模糖尿病α细胞功能障碍.

Swikriti Shrestha1, Lauren T Jennings1, Kyle Knofczynski1

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概括
此摘要是机器生成的。

干细胞衍生阿尔法细胞暴露于内细胞网膜压力模仿糖尿病功能障碍,包括葡萄糖过分分泌. 一种氨酸激酶抑制剂sunitinib保护了这些细胞,为糖尿病研究提供了一种新模式.

关键词:
这就是GLP-1.在PC1/3中使用PC1/3在PC2中,PC2是PC2.在PCSK1中.在PCSK2中使用PCSK2.在SC-α细胞中.格利辛丁是一种甘素.葡萄糖是一种葡萄糖.类似于葡萄糖的-1进行葡萄糖激素的加工.益荷尔蒙转化酶1的产生益激素转化酶2是什么来自干细胞的阿尔法细胞.

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科学领域:

  • 内分泌学 在内分泌学.
  • 细胞生物学 细胞生物学
  • 糖尿病研究 糖尿病研究

背景情况:

  • 胰腺α细胞功能障碍是糖尿病病理生理学的核心.
  • 糖尿病阿尔法细胞表现出葡萄糖的高分泌,改变了葡萄糖的处理,以及转录基因的变化.
  • 缺乏体外的人类α细胞模型阻碍了对这些缺陷的研究.

研究的目的:

  • 为了研究内质网膜 (ER) 应激对干细胞衍生的α (SC-α) 细胞的影响.
  • 建立一个功能性的体外模型,用于研究糖尿病阿尔法细胞表型.
  • 为了确定纠正α细胞功能障碍的潜在治疗点.

主要方法:

  • 在干细胞衍生的α (SC-α) 细胞中诱导ER压力.
  • 测量葡萄糖和相关的分泌物 (glicentin,GLP-1).
  • 对转录组特征和关键路径表达 (MAFB,糖解,氧化酸化) 的分析.
  • 用苏尼蒂尼布治疗SC-α细胞,苏尼蒂尼布是一种氨酸激酶抑制剂.

主要成果:

  • 在SC-α细胞中,ER压力诱导了葡萄糖的高分泌.
  • 经过ER的压力增加了甘素分泌和葡萄糖类-1 (GLP-1) 表达.
  • ER压力导致糖尿病转录状态,降低MAFB和代谢通路的调节.
  • 苏尼提尼布治疗保护了SC-α细胞免受ER压力诱导的葡萄糖激素过分分泌.

结论:

  • 在SC-α细胞中,ER压力重复了糖尿病阿尔法细胞功能障碍的关键特征.
  • 该SC-α细胞模型为研究糖尿病病理生理学提供了一个平台.
  • 苏尼蒂尼布显示出保护ER压力介导的α细胞功能障碍的潜力.