葡萄糖度调节诱导的多能干细胞对胰岛素产生细胞的分化
Chencheng Wang1,2, Shadab Abadpour1,2, Petter Angell Olsen2,3
1Department of Transplant Medicine, Institute for Surgical Research, Oslo University Hospital, Oslo, Norway.
概括
高度的葡萄糖对于从干细胞中产生功能性胰岛素生成细胞 (IPC) 是必不可少的. 然而,这种方法可能会使某些细胞系的分化恶化,这凸显了糖尿病研究中需要仔细考虑的必要性.
科学领域:
- 干细胞生物学 干细胞生物学
- 内分泌学 在内分泌学.
- 代谢性疾病研究研究.
背景情况:
- 人类诱导的多能干细胞 (hiPSCs) 通过产生胰岛素生成细胞 (IPCs) 为糖尿病治疗提供了前景.
- 当前的协议通常使用高度的葡萄糖,但它们对IPC差异化效率和功能的影响尚未完全理解.
- 葡萄糖度在差异化中的有效性在不同的hiPSC线上有所不同.
研究的目的:
- 调查高 (20毫米) 与低 (5.5毫米) 葡萄糖度对三条hiPSC线的IPC差异的影响.
- 确定葡萄糖水平如何影响基因表达 (PDX1,NKX6.1,ABCC8) 和线粒体功能在分化过程中.
- 在不同的葡萄糖条件下评估差异化IPC的功能能力 (葡萄糖刺激的胰岛素分泌,KATP通道活性).
主要方法:
- 用高和低葡萄糖度将三条hiPSC线分成IPC.
- 使用RT-qPCR进行基因表达 (PDX1,NKX6.1,ABCC8) 的定量分析.
- 使用海马XF分析评估线粒体呼吸.
- 测量葡萄糖刺激胰岛素分泌 (GSIS) 和KATP通道活性.
主要成果:
- 在两个hiPSC系中,高葡萄糖通过降低NKX6.1+细胞生成和PDX1共同表达,损害了IPC分化,这与NKX6.1基因激活不足和线粒体呼吸能力减弱有关.
- 在第三个可分化的hiPSC线上,葡萄糖度没有显著改变PDX1/NKX6.1表达或分化的效率.
- 具有葡萄糖刺激胰岛素分泌,增强KATP通道活性和足够的ABCC8基因表达的功能性IPCs仅在高葡萄糖条件下在可接受细胞系中产生.
结论:
- 在分化过程中高葡萄糖度对于产生功能性IPC至关重要,特别是在可分化的hiPSC线条中.
- 高葡萄糖的有益作用是细胞系依赖的;它可以加剧不可改变的hiPSC系的分化失败.
- 根据hiPSC线路特征优化葡萄糖度对于糖尿病研究和治疗中成功生成IPC至关重要.
相关概念视频
iPS Cell Differentiation
2.7K
The ability of induced pluripotent stem cells or iPSCs to differentiate into most body cell types has stimulated repair and regenerative medicine research over the past few decades. iPSC-derived blood cells, hepatocytes, beta islet cells, cardiomyocytes, neurons, and other cell types can repair injuries or regenerate damaged tissue in diseases such as diabetes and neurodegenerative disorders.
2.7K
Induced Pluripotent Stem Cells
23.0K
Stem cells are undifferentiated cells that divide and produce different types of cells. Ordinarily, cells that have differentiated into a specific cell type are post-mitotic—that is, they no longer divide. However, scientists have found a way to reprogram these mature cells so that they “de-differentiate” and return to an unspecialized, proliferative state. These cells are also pluripotent like embryonic stem cells—able to produce all cell types—and are therefore...
23.0K
Hormones Regulating Blood Glucose
3.4K
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...
In addition to accelerating glucose uptake and utilization, insulin has...
3.4K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.3K
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...
Insulin and C-peptide are...
1.3K


