通过光介导增强光遗传工程人类胰腺β细胞的葡萄糖刺激胰岛素释放
Zijing Chen1, Demetrios M Stoukides1, Emmanuel S Tzanakakis1,2,3,4
1Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, United States.
ACS synthetic biology
|February 20, 2024
概括
通过光遗传工程的人类β细胞可以通过使用光来增强葡萄糖刺激胰岛素分泌 (GSIS). 这种光激活方法通过改善血糖控制,为糖尿病提供了一种新的治疗策略.
科学领域:
- 生物技术是生物技术.
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
背景情况:
- 胰腺β细胞对于血糖调节至关重要.
- 1型和2型糖尿病涉及胰岛素分泌受损.
- 光遗传学提供了对细胞功能的精确控制.
研究的目的:
- 为了设计人类β细胞以进行光控制的胰岛素分泌.
- 为了研究光增强葡萄糖刺激胰岛素分泌 (GSIS) 的可行性.
- 在糖尿病小鼠模型中评估光遗传修饰β细胞的治疗潜力.
主要方法:
- 人类EndoC-βH3β细胞被设计成表达蓝光激活的可光激活的腺环酶 (PAC).
- 伪岛屿 (PI) 被制造和转换,以实现高PAC表达 (>80%).
- 在体外和体外研究评估了糖尿病小鼠光激活时细胞内循环腺单酸盐 (cAMP) 水平和GSIS.
主要成果:
- 在工程β细胞中,PAC的光激活迅速增加了细胞内cAMP水平.
- 与非工程细胞相比,暴露于光线导致GSIS的放大>2倍.
- 工程β细胞PI在照明后改善了糖尿病小鼠的葡萄糖耐受性.
- 增强的GSIS保持了双相模式,而不会影响氧气消耗.
结论:
- 用PAC对β细胞的光遗传工程可以通过光控制增强GSIS.
- 这种方法表明了改善糖尿病治疗的潜力,并具有精确的控制.
- 光遗传学提供了一个非药理学的策略,以定制贝塔细胞功能用于糖尿病治疗.
相关概念视频
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
Insulin Secretory Vesicles
5.0K
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...
5.0K
Hormones Regulating Blood Glucose
3.3K
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...
3.3K
Insulin: Biosynthesis, Chemistry, and Preparation
377
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
377


