阿波利波蛋白L基因是β细胞中炎症的新型媒介
Miriam Paz-Barba1, Amadeo Muñoz Garcia1, Twan J J de Winter1
1Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Diabetologia
|November 4, 2023
概括
在炎症和2型糖尿病期间,胰腺β细胞中的Apolipoprotein L (APOL) 基因受到上调. 这些基因在β细胞损伤中发挥作用,为糖尿病发展提供了新的见解.
科学领域:
- * 分子生物学和免疫学
- *内分泌学和代谢性疾病
背景情况:
- *炎症是已知的β细胞功能障碍和死亡的驱动因素,但精确的分子机制尚未完全理解.
- *阿波利波蛋白L (APOL) 基因家族与先天性免疫,亡,代谢综合征和2型糖尿病 (T2DM) 有关.
研究的目的:
- * 调查APOL基因在炎症诱导的β细胞损伤中的作用.
- * 探索APOL基因对T2DM病变发生的潜在贡献.
主要方法:
- *在压力条件下分析来自人类胰腺小岛细胞的单细胞RNA测序 (scRNAseq) 数据集.
- * 在EndoC-βH1细胞和初级人类小岛中进行验证.
- *功能损失和功能增益实验,以确定β细胞中的APOL基因功能.
主要成果:
- *APOL基因在人类β细胞中表达,并在炎症期间通过Janus激酶 (JAK) -信号转换器和转录激活器 (STAT) 途径进行上调.
- *APOL1的过度表达加剧了内质网膜的压力;APOL1的敲击防止了细胞因子诱导的β细胞死亡.
- *与非糖尿病捐赠者相比,T2DM捐赠者的β细胞中APOL基因升高.
结论:
- *APOL蛋白被确定为岛屿炎症的新型调节者.
- *APOL基因可能在β细胞损伤中发挥重要作用,有助于糖尿病的发展.
- * 针对APOL途径可以为T2DM提供治疗策略.
相关概念视频
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
Cell Specific Gene Expression
13.6K
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...
13.6K
Glucagon-like Receptor Agonists
332
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
332
Insulin: The Receptor and Signaling Pathways
1.2K
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...
1.2K
Inflammation
53.7K
Overview
53.7K
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


