从只含有β细胞的小岛中调节和适应体内胰岛素分泌
Marta Perez-Frances1, Eva Bru-Tari1, Christian Cohrs2,3
1Department of Genetic Medicine and Development, iGE3 and Centre facultaire du diabète, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Nature metabolism
|August 21, 2024
概括
胰腺非β细胞对于胰岛素分泌或血糖控制并不重要. 研究表明,仅β细胞就能维持葡萄糖平衡,从而支持新的糖尿病治疗方法.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 代谢疾病 代谢疾病
背景情况:
- 胰腺小岛含有产生胰岛素的β细胞和其他产生激素的非β细胞 (α,delta,gamma).
- 对于非β细胞对于精确的胰岛素分泌和葡萄糖调节的必要性仍然不完全理解.
研究的目的:
- 研究非β细胞在调节β细胞功能和整体葡萄糖平衡中的作用.
- 为了确定仅由β细胞组成的小岛是否能够维持正常的代谢功能.
主要方法:
- 研究了基因改造小鼠与成年小岛只含有β细胞.
- 使用了仅由初级β细胞组成的人类伪岛屿.
- 评估血糖调节,耐葡萄糖,胰岛素敏感性和体重变化.
- 分析了胰岛素分泌动态,线粒体呼吸和对exendin-4的反应.
主要成果:
- 缺乏非β细胞的小鼠表现出最佳的血糖调节,增强的葡萄糖耐受性和改善的胰岛素敏感性.
- 这些小鼠在高脂肪饮食中表现出受限的体重增加.
- 仅由β细胞组成的岛屿表现出与完整岛屿相比的胰岛素分泌动态.
- 人类β细胞伪岛屿保持了葡萄糖调节的功能,包括线粒体呼吸和胰岛素分泌.
结论:
- 非β细胞对于维持血糖平衡和β细胞功能是不可或缺的.
- 这些发现支持开发缺乏非β细胞的β细胞集群,用于糖尿病治疗策略.
- 潜在的治疗方法包括干细胞的体外分化或非β细胞的现场重编程.
相关概念视频
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.2K
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...
1.2K
Insulin Secretory Vesicles
4.9K
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...
4.9K
Insulin: Biosynthesis, Chemistry, and Preparation
365
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...
365
Hormones Regulating Blood Glucose
3.2K
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...
3.2K
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
Cells and Secretions of the Pancreas
2.1K
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...
2.1K


