在胰岛素分泌和适应性β细胞增殖中IGF2R的调节作用
Jun Shirakawa1,2,3, Dario F De Jesus1,4, Takahiro Tsuno2
1Islet Cell and Regenerative Biology, Joslin Diabetes Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA.
Diabetes
|October 3, 2025
概括
胰岛素样生长因子-2受体 (IGF2R) 调节胰岛素分泌,细胞增殖和胰腺β细胞的自. 缺少IGF2R会损害葡萄糖耐受性和胰岛素分泌,强调其在糖尿病中的作用.
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:
- 胰岛素样生长因子-2受体 (IGF2R) 在胰腺β细胞功能中的作用尚不清楚.
- 已知IGF2R用于 lysosomal酶运输和IGF2清除.
研究的目的:
- 用体外和体外模型研究IGF2R在β细胞生物学中的直接作用.
- 确定IGF2R缺乏对胰岛素分泌,细胞增殖和自的影响.
主要方法:
- 在β细胞系 (IGF2RKD) 中的IGF2R的体外淘汰.
- 在体内生成特莫西芬诱导性β细胞特异性IGF2R淘汰赛小鼠.
- 评估葡萄糖耐受性,胰岛素分泌,β细胞质量和自标志物 (p62,LC3B,ULK1).
主要成果:
- 在β细胞中IGF2R的淘汰减少了葡萄糖诱导的胰岛素分泌和增加了增殖.
- 贝塔细胞特异性IGF2R淘汰赛小鼠显示葡萄糖耐受性受损,胰岛素分泌量减弱.
- 缺少IGF2R导致自细胞形成减少和自细胞标志物受损.
- 在2型糖尿病岛屿中观察到IGF2R功能降低和m6A甲基化.
结论:
- IGF2R是胰岛素分泌,β细胞增殖和自的关键调节者.
- 失调IGF2R有助于β细胞功能受损,并可能在2型糖尿病中发挥作用.
相关概念视频
Insulin: The Receptor and Signaling Pathways
2.8K
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...
2.8K
Hormones Regulating Blood Glucose
6.4K
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...
6.4K
TGF - β Signaling Pathway
10.5K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
10.5K
PI3K/mTOR/AKT Signaling Pathway
5.3K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.3K
Insulin Secretory Vesicles
6.4K
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...
6.4K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
2.2K
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...
2.2K


