持续高血糖症特别针对mRNAs的翻译,以分泌胰岛素
The Journal of clinical investigation
|November 30, 2023
概括
慢性高葡萄糖会损害胰腺β细胞功能,抑制参与胰岛素分泌的关键基因的翻译,而不仅仅是胰岛素本身. 这影响了对β细胞功能至关重要的蛋白质水平.
科学领域:
- * 分子生物学 * 分子生物学
- * 内分泌学 在内分泌学.
- * 糖尿病研究研究
背景情况:
- * 胰腺β细胞将葡萄糖代谢与胰岛素的产生和分泌联系起来.
- * 糖尿病慢性高葡萄糖会损害胰岛素分泌和胰岛素翻译.
- *持续高葡萄糖对β细胞中其他关键基因转换的影响尚不清楚.
研究的目的:
- * 为了研究持续高葡萄糖对β细胞mRNA翻译的全基因组影响.
- * 识别慢性高血糖在转化水平上受慢性高血糖影响的特定基因和途径.
- * 了解糖尿病中β细胞功能障碍背后的调节机制.
主要方法:
- * 在MIN6胰岛素瘤细胞中利用高通量核糖体分析和新生蛋白质组学.
- *在持续高葡萄糖条件下分析的mRNA翻译变化.
- * 验证了初级大鼠和人类小岛和体内高血糖模型的验证结果.
主要成果:
- *持续高葡萄糖抑制葡萄糖刺激的胰岛素分泌.
- * 胰岛素和参与胰岛素分泌颗粒形成的mRNA的向下调节的翻译,外细胞和代谢合分泌.
- * 在高血糖的ex vivo和in vivo模型中观察到类似的翻译下调.
- * 对于翻译下调的基因而言,细胞蛋白质丰度降低.
结论:
- *发现了一种转化调节电路,有助于β细胞葡萄糖毒性.
- * 证明慢性高葡萄糖严重损害了对β细胞功能至关重要的蛋白质的表达.
- * 在糖尿病的翻译水平上确定了β细胞功能障碍的新机制.
相关概念视频
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
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
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: The Receptor and Signaling Pathways
1.2K
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...
1.2K
Hypoglycemia and Glucagon
272
Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
272
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


