胰岛素阳性细胞群的丧失会导致1型糖尿病的岛屿频率和β细胞面积的减少
Denise M Drotar1, Giovanni J A Vazquez Ramos1, MacKenzie D Williams1
1Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida Diabetes Institute, Gainesville, FL.
Diabetes
|July 24, 2025
概括
在1型糖尿病 (T1D) 中,较小的胰岛素阳性细胞和细胞群在疾病发育早期优先丢失,而较大的岛屿仍然保留. 这一发现对于理解T1D进展和制定干预措施至关重要.
科学领域:
- 内分泌学 在内分泌学.
- 免疫学 免疫学 免疫学
- 病理学 病理学 病理学
背景情况:
- 1型糖尿病 (T1D) 涉及免疫介导的胰岛素生成β细胞的破坏.
- 贝塔细胞损失的确切时间和性质,特别是在早期的T1D中,尚未完全理解.
- 识别小岛组成的早期变化是制定阻止T1D进展的战略的关键.
研究的目的:
- 调查T1D发展期间胰腺小岛大小和细胞组成的变化.
- 为了确定哪些特定的岛屿组件在T1D的进展中首先丢失.
- 分析自身抗体阳性和疾病持续时间对小岛结构的影响.
主要方法:
- 开发了一个全幻灯片图像分析管道,用于对胰腺组织进行定量评估.
- 分析了来自没有糖尿病的捐赠者,具有自身抗体阳性和T1D不同持续时间的145个人类胰腺.
- 量化内分泌区域,小岛频率,小岛间距离和内分泌物体大小分布.
主要成果:
- 与对照组相比,T1D胰腺显示出岛屿频率下降和岛屿间距离增加.
- 在T1D发病时观察到胰岛素阳性 (INS+) 单细胞,细胞群和中小型岛屿的显著损失.
- 大型INS+小岛 (>200μm) 保存,甚至在多个自身抗体阳性捐赠者中也注意到INS+小岛分数的变化.
- 这些发现表明,在T1D早期,较小的INS+内分泌物体的偏好性损失.
结论:
- 早期的T1D的特点是较小的胰岛素阳性内分泌细胞和细胞群的偏好性损失.
- 较大的小岛的保存表明,较小的结构对T1D的自身免疫破坏具有特定的脆弱性.
- 这些见解对于理解T1D病原体和设计有针对性的治疗干预措施至关重要.
相关概念视频
Diabetes Mellitus: Overview and Type I Subtype
3.3K
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels due to inadequate insulin production, insulin resistance, or both. The condition affects millions worldwide and can significantly impact their health and quality of life.
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. As a result, the body is unable to produce sufficient insulin, and individuals with...
3.3K
Carbohydrate Metabolism
11.8K
Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
11.8K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.4K
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...
1.4K
Pathophysiology of Diabetes
1.2K
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. The four categories of diabetes are type 1 diabetes, type 2 diabetes, other specific types of diabetes, and gestational diabetes.
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility,...
1.2K
Diabetes Mellitus: Type 2 and Gestational
3.0K
Type 2 diabetes, characterized by insulin resistance, arises when the insulin receptors on cells lose responsiveness to insulin, diminishing the cell's capacity to take up glucose, resulting in elevated blood glucose levels. To receive a diagnosis of Type 2 diabetes, a series of blood glucose tests are necessary to assess whether the blood glucose falls within normal parameters. If the result is out of the normal range, a patient may be diagnosed as prediabetic or diabetic, depending on the...
3.0K
Insulin Secretory Vesicles
5.4K
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...
5.4K


