葡萄糖诱导的铁载体调节意味着脏的铁积累
Rajiv Kumar1, Diksha Kulshreshtha2, Ayushi Aggarwal3
1Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067, India; All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110034, India.
Biochimica et biophysica acta. General subjects
|September 15, 2024
概括
糖尿病的高葡萄糖水平会增加铁的吸收,并减少细胞的铁出口,导致铁的积累和潜在的损伤. 这项研究揭示了糖尿病脏铁失调的关键机制.
科学领域:
- 腎臟病學 (nephrology) 是一種醫學.
- 代谢障碍 代谢障碍 代谢障碍
- 铁的新陈代谢 铁的新陈代谢
背景情况:
- 糖尿病病与铁含量增加有关.
- 驱动糖尿病脏铁积累的确切机制尚不清楚.
- 了解铁失调对于治疗糖尿病病至关重要.
研究的目的:
- 为了阐明在糖尿病条件下脏中铁积累的分子机制.
- 为了研究葡萄糖,转移素受体1 (TFRC) 和铁波丁 (FPN) 在糖尿病铁稳定中的作用.
- 探索肝素独立途径在葡萄糖诱导的FPN降解中的参与.
主要方法:
- 使用细胞进行体外研究,以评估葡萄糖对TFRC和FPN表达和降解的影响.
- 针对FPN的局部导向突变发生,以调查Cys-326在葡萄糖诱导的降解中的作用.
- 在体内研究使用链子素 (STZ) 诱导的糖尿病大鼠模型来分析铁平衡成分.
- 使用了西斑,免疫组织化学,珀尔斯染色和非血红素铁估计.
主要成果:
- 葡萄糖通过细胞的转化控制来提高TFRC的调节来增加铁的吸收.
- 葡萄糖通过 hepcidin 独立的机制促进 FPN 降解,从而降低铁出口.
- 患有高血糖的老鼠表现出TFRC增加,FPN降低,以及中的铁水平升高.
- 肝素mRNA水平在脏中没有显著变化,但在肝脏中略有下降.
结论:
- 高血糖水平通过调节TFRC和FPN来破坏脏铁运输的调节.
- 这些变化导致糖尿病患者脏中大量的铁积累.
- 这些发现表明,在糖尿病中预防与铁相关的损伤的新型治疗标.
相关概念视频
Glucose Transporters
22.6K
Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
22.6K
Glucose Absorption Into the Small Intestine
31.4K
Complex carbohydrates consumed cannot be absorbed into the small intestine in their original form. First, they must be hydrolyzed to a monosaccharide form such as glucose or galactose. These monosaccharides are then transported across the intestinal membrane and into the blood via transcellular transport. The intestinal epithelial cells allow the movement of these monosaccharides with a defined 'entry' through membrane transporter proteins present on their apical membrane and...
31.4K
The Early Endosome: Endocytosis of Transferrin
3.2K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
3.2K
Secondary Active Transport
6.9K
One example of how cells use the energy contained in electrochemical gradients is demonstrated by glucose transport into cells. The ion vital to this process is sodium (Na+), which is typically present in higher concentrations extracellularly than in the cytosol. Such a concentration difference is due, in part, to the action of an enzyme "pump" embedded in the cellular membrane that actively expels Na+ from a cell. Importantly, as this pump contributes to the high concentration of...
6.9K
Glucose Homeostasis: Regulation of Blood Glucose
1.5K
Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
1.5K
Hormones Regulating Blood Glucose
3.1K
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...
3.1K


