一种FABP4和核酸激酶的激素复合体调节岛屿功能
Kacey J Prentice1, Jani Saksi1, Lauren T Robertson1
1Sabri Ülker Center for Metabolic Research, Harvard T. H. Chan School of Public Health, Department of Molecular Metabolism, Boston, MA, USA.
Nature
|December 9, 2021
概括
脂肪酸结合蛋白4 (FABP4) 形成一种新型的荷尔蒙复合物,Fabkin,调节能量平衡和β细胞功能. 针对这种复合体有望预防1型和2型糖尿病.
科学领域:
- 内分泌学和新陈代谢
- 分子生物学
- 心血管研究
背景情况:
- 脂肪细胞的能量储存释放至关重要,但与胰岛素抵抗相关的脂质分解失调会破坏新陈代谢平衡.
- 循环脂肪酸结合蛋白4 (FABP4) 水平与心脏代谢疾病相关,但其作用机制尚不清楚.
研究的目的:
- 阐明激素FABP4的作用机制.
- 研究FABP4在调节细胞外ATP/ADP水平及其对β细胞的影响.
- 探索针对FABP4复合物的潜力,以预防代谢疾病.
主要方法:
- 研究了涉及FABP4,腺激酶 (ADK) 和核二酸激酶 (NDPK) 的功能激素复合物的形成.
- 评估了该复合体对细胞外ATP和ADP水平的调节.
- 在糖尿病模型中评估了FABP4复合物的抗体中介向对代谢结果和β细胞功能的影响.
主要成果:
- 证明激素FABP4与ADK和NDPK形成一个称为Fabkin的复合物,该复合物调节细胞外ATP和ADP.
- 确定了Fabkin复合体对β细胞的显著影响,这表明它在脂肪β细胞内分泌轴中发挥作用.
- 显示Fabkin复合体的抗体中介向改善了代谢健康,增强了β细胞功能,并保持了β细胞的完整性.
结论:
- FABP4-ADK-NDPK复合体 (Fabkin) 是一种新兴的调节能量稳态和器官代谢功能的激素.
- 作为脂肪β细胞轴的关键调节剂,Fabkin影响脂解和β细胞功能.
- 针对Fabkin复合体提供了一种有前途的治疗策略,用于预防1型和2型糖尿病以及其他代谢疾病.
相关概念视频
Insulin Secretory Vesicles
5.9K
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...
5.9K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.5K
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...
1.5K
Insulin: The Receptor and Signaling Pathways
1.7K
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...
1.7K
Hormones Regulating Blood Glucose
4.7K
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...
4.7K
Insulin: Biosynthesis, Chemistry, and Preparation
653
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment...
653
Cell Specific Gene Expression
14.2K
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...
14.2K


