在β细胞上的C3aR1增强了β细胞的功能和生存,以维持葡萄糖平衡
Renan Pereira de Lima1, Ang Li1, Ankit Gilani1
1Division of Cardiology, Weill Center for Metabolic Health, Cardiovascular Research Institute, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.
Molecular metabolism
|April 6, 2025
概括
胰腺β细胞需要C3aR1才能在2型糖尿病 (T2D) 中正常功能和生存. C3aR1的丧失会损害胰岛素分泌和β细胞质量,突出其在T2D病变发生过程中的关键作用.
科学领域:
- 免疫学 免疫学 免疫学
- 内分泌学 在内分泌学.
- 代谢疾病 代谢疾病
背景情况:
- 胰腺β细胞功能障碍是2型糖尿病 (T2D) 发展的关键因素.
- 以前的研究表明,β细胞上的C3aR1支持胰岛素分泌和生存.
- 全身C3aR1淘汰模型由于广泛表达,限制了对直接β细胞影响的理解.
研究的目的:
- 在T2D条件下阐明C3aR1在胰腺β细胞中的特定作用.
- 研究C3aR1对β细胞功能和质量的直接影响.
- 评估C3aR1在人类小岛上的转化相关性.
主要方法:
- 产生β细胞特异的C3aR1淘汰赛小鼠 (β-C3aR1 KO).
- 评估葡萄糖平衡,β细胞功能和在代谢压力下的质量.
- 来自对照和β-C3aR1 KO小鼠的小岛的蛋白质组分析.
- 在人类小岛中评估C3AR1对葡萄糖刺激胰岛素分泌的评估.
主要成果:
- 在小鼠中,β细胞特异性的C3aR1缺失会恶化葡萄糖耐受性,降低胰岛素水平.
- 在高脂肪饮食下,β-C3aR1 KO小鼠表现出降低的β细胞质量和受损的胰岛素分泌.
- 失去C3aR1会增加β细胞对脂毒性的敏感性,并改变身份/压力标志物.
- 蛋白质组学揭示了C3aR1缺乏β细胞中的MAPK通路和线粒体功能障碍.
- C3AR1与人类小岛的胰岛素分泌有积极的相关性.
结论:
- 胰腺β细胞上的C3aR1对于维持T2D中的功能和质量至关重要.
- 向C3aR1可能提供一种治疗策略,以保持T2D中的β细胞健康.
相关概念视频
Hormones Regulating Blood Glucose
2.9K
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...
2.9K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.0K
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...
1.0K
Cell Specific Gene Expression
13.3K
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...
13.3K
Glucose Homeostasis: Regulation of Blood Glucose
1.3K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
1.3K
Insulin Secretory Vesicles
4.8K
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...
4.8K
Overview of Carbohydrate Metabolism
582
Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to living cells. The most important carbohydrate is glucose, which can be broken down via glycolysis to enter into the Krebs cycle and eventually lead to the production of ATP through oxidative phosphorylation.
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
582


