NERP-4-SNAT2轴调节胰腺β细胞的维护和功能
Weidong Zhang1,2, Ayako Miura2,3, Md Moin Abu Saleh2,4
1Department of Bioregulatory Sciences, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
Nature communications
|December 9, 2023
概括
神经内分泌调节-4 (NERP-4) 通过刺激胰腺β细胞的氨基酸吸收来增强胰岛素分泌. 这种胺氨基酸输送轴对于β细胞的功能和维护至关重要.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 代谢过程中的代谢.
背景情况:
- 胰腺β细胞的胰岛素分泌受到各种因素的调节,包括营养素和激素.
- 氨基酸通过β细胞上的特定载体影响胰岛素分泌.
- VGF蛋白及其衍生的,NERP-4,在β细胞功能中起作用.
研究的目的:
- 研究NERP-4在调节胰岛素分泌和β细胞功能的作用.
- 阐明NERP-4影响β细胞的机制,重点关注氨基酸运输.
- 为了确定NERP-4能否在糖尿病模型中保护β细胞.
主要方法:
- 从转基因小鼠的胰腺组织中测量Ca2+的流入.
- 从孤立的人类和小鼠小岛和β细胞系中评估葡萄糖刺激的胰岛素分泌.
- 评估NERP-4对db/db小鼠β细胞功能和线粒体活性的影响.
- 研究NERP-4与结合的中性氨基酸载体2 (SNAT2) 的相互作用及其对氨基酸吸收的影响.
- 检查SNAT2删除或抑制对NERP-4保护作用的后果.
主要成果:
- 在各种模型中,NERP-4增加了Ca2+的流入,并增强了葡萄糖刺激的胰岛素分泌.
- 通过促进线粒体功能和减少代谢压力,NERP-4的使用改善了db/db小鼠的β细胞维护和功能.
- 通过对SNAT2的作用,NERP-4刺激胰岛素分泌,增加了谷氨酸,氨酸和氨酸的吸收.
- 删除或抑制SNAT2取消了NERP-4对β细胞维护的保护作用.
结论:
- NERP-4代表了一种用于调节β细胞功能和维护的新型自克林机制.
- 氨基酸输送轴,特别是涉及NERP-4和SNAT2,对于β细胞的健康至关重要.
- 对于涉及β细胞功能障碍的疾病,NERP-4具有潜在的治疗价值.
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
Cells and Secretions of the Pancreas
2.2K
The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
Concurrently, the dispersed clusters of endocrine cells throughout the...
2.2K
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
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
Regulation of Food Intake
239
Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
239
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


