卡路里限制调节β细胞IP3R活动以调节Ca2+恒温和细胞网络连接
Johannes Pfabe1, Cristiane Dos Santos2, Melanie Cutler2
1Institute of Physiology, Center for Physiology and Pharmacology and Comprehensive Center for AI in Medicine, Medical University of Vienna, Austria 1090.
bioRxiv : the preprint server for biology
|September 15, 2025
概括
卡路里限制 (CR) 通过改变 (Ca2+) 信号和保护ER Ca2+压力来增强β细胞功能. 这改善了β细胞的适应性和寿命,为CR提供了新的见解.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 代谢研究研究 代谢研究
背景情况:
- 卡路里限制 (CR) 可以延长寿命并改善代谢健康.
- 抗胰岛素增强β细胞 (胰岛素生成细胞) 的寿命和功能.
- CR对β细胞 (Ca2+) 稳态和胰岛素分泌的影响尚不清楚.
研究的目的:
- 研究CR如何影响β细胞Ca2+动态和网络连接.
- 为了了解CR诱导的β细胞Ca2+信号传递的变化背后的机制.
- 阐明Ca2+稳态在CR介导的β细胞适应中的作用.
主要方法:
- 使用来自ad-libitum (AL) 和CR小鼠的急性胰腺组织切片.
- 使用低亲和度Ca2+指标进行快速共焦成像,监测细胞质Ca2+梯度.
- 半自动分析确定了单个β细胞和Ca2+升事件.
主要成果:
- 红细胞β细胞表现出快速,短幅度的Ca2+振荡.
- 红细胞β细胞在岛屿内显示出大部分断开的网络活动.
- 乙胆刺激揭示了CRββ细胞中较快的IP3R驱动的Ca2+振荡,这与较高的cAMP水平有关.
- 红细胞β细胞证明了对ER Ca2+压力的保护.
结论:
- CR改变了β细胞的Ca2+信号,导致了不同的网络动态.
- 升高的cAMP水平和更快的Ca2+振荡保护CRβ细胞免受ERCa2+压力.
- 这项研究提供了对β细胞适应卡路里限制的机制性见解.
相关概念视频
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
Cell Specific Gene Expression
16.3K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
16.3K
Feedback Regulation of Calcium Concentration
3.9K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.9K
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
6.5K
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...
6.5K
Calmodulin-dependent Signaling
6.0K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
6.0K


