西尔德纳菲尔增强了胰腺β细胞中的流和胰岛素分泌
Naoya Murao1,2, Risa Morikawa1, Yusuke Seino1,2
1Department of Endocrinology, Diabetes and Metabolism, School of Medicine, Fujita Health University, Toyoake, Japan.
Physiological reports
|June 11, 2024
概括
西尔德纳菲尔通过胰腺β细胞的R型通道增加的流入来增强胰岛素分泌. 这独立于PDE5/cGMP通路发生,这表明潜在的抗糖尿病应用的新机制.
科学领域:
- 内分泌学 在内分泌学.
- 细胞生物学 细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 西尔德纳菲尔 (一种PDE5抑制剂) 改善了胰岛素敏感性,但其对胰岛素分泌的影响还未得到充分研究.
- 了解西尔德纳菲尔对胰腺β细胞功能的影响,对于探索其治疗潜力至关重要.
研究的目的:
- 为了研究西尔代纳菲尔对MIN6-K8小鼠克隆β细胞中的胰岛素分泌的影响.
- 阐明特定的离子通道机制和信号通路,涉及到西尔代纳菲尔诱导的胰岛素分泌.
主要方法:
- 使用了MIN6-K8小鼠克隆β细胞和KATP通道缺陷β细胞.
- 评估胰岛素分泌和 (Ca2+) 流入.
- 使用电压依赖通道 (VDCC) 的药理抑制剂和PDE5敲击.
主要成果:
- 西尔德纳菲尔通过增强Ca2+流入以去极化依赖的方式扩大胰岛素分泌.
- 这种影响独立于KATP通道,主要涉及R型VDCC.
- 该机制在很大程度上独立于基化酶-5 (PDE5) /循环GMP (cGMP) 途径.
结论:
- 西尔德纳菲尔作为一种胰岛素变剂,通过R型VDCCs刺激胰岛素分泌,独立于PDE5/cGMP通路.
- 这种新的机制表明了西尔德纳菲尔作为抗糖尿病药物的潜力.
- 这些发现为调节胰岛素分泌提供了新的见解.
相关概念视频
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
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
Hormones Regulating Blood Glucose
3.2K
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...
3.2K
Calmodulin-dependent Signaling
5.1K
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,...
5.1K
cAMP-dependent Protein Kinase Pathways
6.3K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.3K
Feedback Regulation of Calcium Concentration
3.4K
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...
3.4K


