对黄素对β细胞活力和胰岛素分泌的离散毒性的全面调查
Rania Derguine1, Abdelmalek Rezgui2, Rechda Amel Tachour3
1Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, Ferhat ABBAS Setif 1 University (UFAS1), Setif, 19000, Algeria; Biotechnology Research Center (CRBt), Ali Mendjli, Nouvelle Ville UV 03 BP E73 Constantine 25000, Algeria.
概括
高度的黄素对胰腺β细胞有毒,通过氧化应激和ER应激途径诱导亡. 这一发现对于理解黄素至关重要.
科学领域:
- 生物化学 生物化学
- 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:
- 黄素表现出治疗潜力,但其精确的机制,特别是关于胰腺β细胞功能,仍然不清楚.
- 这项研究调查了黄素对胰腺β细胞和小岛的细胞毒性作用.
研究的目的:
- 阐明黄素在胰腺β细胞和小岛上的毒性机制.
- 评估黄素对细胞活力,胰岛素分泌,氧化应激和ER应激的影响.
主要方法:
- 研究了黄素对小鼠中隔离的朗格汉斯小岛以及NIT1β细胞系活力和胰岛素分泌的影响.
- 评估了氧化应激标志物,活性氧物种 (ROS) 生产和未折叠蛋白质响应 (UPR) 基因表达.
- 使用in silico和in vitro方法来确定黄素蛋白相互作用和受影响的途径.
主要成果:
- 在较低度下,黄素可以增强细胞活力和胰岛素分泌.
- 在高度 (60微克/毫升) 中,黄素显著降低β细胞活力 (70-75%) 和胰岛素分泌.
- 黄素诱导氧化应激,增加NFKB1,ATF4和CHOP的表达,并触发ER应激,其效应被STZ联合使用放大.
- 生物信息分析显示,黄素与14种蛋白质相互作用,包括NFkB通路中的蛋白质.
结论:
- 高剂量的黄素对胰腺β细胞表现出细胞毒性.
- 黄素通过ER压力和氧化应激途径诱导β细胞亡.
- NFkB通路和相关蛋白质与黄素诱导的β细胞毒性有关.
相关概念视频
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.0K
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...
1.0K
Insulin Secretory Vesicles
4.8K
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...
4.8K
Hormones Regulating Blood Glucose
2.9K
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...
2.9K
Dipeptidyl Peptidase 4 Inhibitors
140
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
140


