岛内葡萄糖信号调节β细胞连接,第一阶段胰岛素分泌和葡萄糖同质化
K Suba1, Y Patel2, A Martin-Alonso2
1Department of Bioengineering, Imperial College London, London SW7 2AZ, United Kingdom; Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London W12 0NN, United Kingdom.
Molecular metabolism
|April 27, 2024
概括
贝塔细胞中葡萄糖受体的丧失会损害2型糖尿病 (T2D) 中的葡萄糖控制. 葡萄糖模拟治疗恢复了同步的波和胰岛素分泌,这表明T2D的治疗潜力.
科学领域:
- 内分泌学 在内分泌学.
- 代谢疾病 代谢疾病
- 细胞生物学 细胞生物学
背景情况:
- 2型糖尿病 (T2D) 的特点是第一阶段胰岛素分泌受损.
- 岛内葡萄糖受体 (GCGR) 信号在β细胞功能中的作用尚不清楚.
研究的目的:
- 调查岛内GCGR信号在β细胞功能中的作用.
- 在T2D模型中评估GCGR信号对小岛活性和胰岛素分泌的影响.
主要方法:
- 研究的小鼠具有β细胞选择性丧失GCGR (Gcgrβ细胞-/-).
- 使用GCaMP6f指标用于小岛的体外和体内成像.
- 将移植的小岛移植到高脂肪饮食的野生类型小鼠中,并用葡萄糖同类 (GCG-analogue) 进行治疗.
主要成果:
- Gcgrβ-cell-/-小鼠显示葡萄糖耐受性受损,但没有禁食血糖.
- 贝塔细胞中GCGR的丧失导致了小岛的同步波减少,在生物体中部分挽救.
- 移植小岛的饮食引起的高血糖也减少了波,这些波通过独立于体重减轻的GCG-模拟治疗来逆转.
结论:
- 岛内GCGR信号传递对于保持同步的β细胞活性至关重要.
- 葡萄糖激素药物可能提供一种治疗策略,以恢复T2D中的胰岛素分泌能力.
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: 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
Hormones Regulating Blood Glucose
3.3K
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...
3.3K
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
Glucagon-like Receptor Agonists
319
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...
319


