改变BAG3-胰岛素局部化与人类第一阶段胰岛素分泌受损有关
Verena Damiani1, Gianfranco Di Giuseppe2, Giulia Gliozzo3
1Center for Advanced Studies and Technology (CAST), "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy; Department of Innovative Technologies in Medicine and Dentistry, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy; Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Diabetes research and clinical practice
|May 8, 2025
概括
人类胰腺小岛中的高BAG3蛋白水平与第一阶段胰岛素分泌受损有关,这是2型糖尿病 (T2DM) 发展的关键因素. 针对BAG3可能为T2DM提供新的治疗策略.
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:
- 第一个阶段的胰岛素分泌对于早期2型糖尿病 (T2DM) 的发展至关重要.
- BAG3蛋白在人体胰岛素分泌中的作用尚不清楚,尽管它在小鼠模型中被发现.
研究的目的:
- 研究人类胰腺小岛的BAG3表达.
- 确定BAG3水平与β细胞功能之间的关系.
主要方法:
- 分析了来自12名非糖尿病捐赠者的人类胰腺组织.
- 代谢评估包括口服葡萄糖耐受性测试 (OGTT) 和代谢.
- 免疫光和共聚焦显微镜评估了BAG3-胰岛素的局部化.
主要成果:
- 高BAG3表达与明显受损的第一阶段胰岛素分泌相关.
- 在高BAG3个体中观察到OGTT期间降低速率灵敏度和更高的葡萄糖后血葡萄糖水平.
- 在高BAG3患者中,岛屿大小增加,胰岛素/葡萄糖素比率或胰岛素敏感性没有变化.
结论:
- BAG3与人类的第一阶段胰岛素分泌有关,可能通过影响胰岛素颗粒外细胞形成.
- 调节BAG3可能是预防或延迟T2DM发病的治疗点.
相关概念视频
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
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
Insulin: Biosynthesis, Chemistry, and Preparation
318
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...
318
Insulin: The Receptor and Signaling Pathways
1.0K
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...
1.0K
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


