从Cdk5激活剂p35中衍生的一种体TFP5,保护胰腺β细胞免受葡萄糖毒性影响
S-Y Liu1,2, S-L Cao1,2, H-Y Luo1,2
1Department of Nephrology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China.
Bulletin of experimental biology and medicine
|December 12, 2023
概括
TFP5是一种新型,通过抑制Cdk5过活,增强胰岛素分泌,减少胰腺小岛炎症和亡,有效治疗2型糖尿病.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 内分泌学 在内分泌学.
背景情况:
- 循环素依赖性激酶5 (Cdk5) 过活性与2型糖尿病 (T2DM) 病原发生有关.
- 胰腺β细胞功能障碍和炎症有助于T2DM进展.
研究的目的:
- 为了合成和评估TFP5的治疗潜力,一种新的Cdk5抑制剂,用于T2DM.
- 研究TFP5对Cdk5活性,胰岛素分泌,β细胞亡和胰腺小岛炎症的影响,在体外和体内.
主要方法:
- 通过与FITC和TAT域结合p5 (p35蛋白衍生物) 合成的TFP5.
- 用不同度的葡萄糖 (5或25毫米) 处理的MIN6细胞 (老鼠小岛β细胞).
- 在C57BL/6J (对照) 和db/db (T2DM) 小鼠进行的体内研究.
主要成果:
- TFP5有效地抑制了病理性的Cdk5过活.
- TFP5增强了胰岛素分泌,并保护胰腺β细胞免受亡.
- 在胰腺小岛中,TFP5降低了炎症性细胞因子表达 (TGF-β1,TNFα,IL-1β).
结论:
- 通过针对Cdk5.5,TFP5显示了T2DM的显著治疗潜力.
- TFP5对胰腺β细胞表现出保护作用,并减少小岛炎症.
- TFP5代表了对2型糖尿病的有前途的新疗法候选者.
相关概念视频
Cell Specific Gene Expression
13.6K
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...
13.6K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.3K
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...
1.3K
Insulin Secretory Vesicles
5.0K
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...
5.0K
Hormones Regulating Blood Glucose
3.4K
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...
3.4K
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
cAMP-dependent Protein Kinase Pathways
6.4K
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,...
6.4K


