相关实验视频
Updated: Jul 13, 2026

11:10
Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice
Published on: November 16, 2011
通过FOXO1-PGC-1alpha相互作用进行胰岛素调节的肝脏葡萄糖生成
Pere Puigserver1, James Rhee, Jerry Donovan
1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature
|May 20, 2003
概括
肝脏葡萄糖生成,对于禁食生存至关重要,由FOXO1和PGC-1alpha.regulated调节. 这些因素相互作用,控制肝脏中胰岛素调节的葡萄糖生产.
科学领域:
- 代谢调节 代谢调节 代谢调节
- 分子生物学分子生物学
- 内分泌学 在内分泌学.
背景情况:
- 肝脏葡萄糖生成对于禁食期间的生存至关重要,但在糖尿病中失调.
- 葡萄糖皮质醇和葡萄糖激活肝脏葡萄糖生成,而胰岛素抑制它.
- FOXO1和PGC-1α是关键的调节剂,但它们的相互作用尚不清楚.
研究的目的:
- 阐明FOXO1和PGC-1alpha在调节肝脏葡萄糖生成中的协作机制.
- 研究Akt介导酸化在FOXO1-PGC-1α相互作用中的作用.
- 通过FOXO1.1.确定胰岛素对通过PGC-1alpha刺激的葡萄糖产生的影响.
主要方法:
- 在细胞和小鼠模型中利用野生类型和突变FOXO1等位基因.
- 研究了FOXO1.1的PGC-1α结合和协同激活.
- 评估了胰岛素对PGC-1alpha刺激的葡萄糖生成在修改后的FOXO1.1存在时的影响.
主要成果:
- PGC-1alpha 结合并协同激活FOXO1,这是由Akt酸化抑制的过程.
- 福克索1对于PGC-1α介导的葡萄糖原基因表达的诱导至关重要.
- 胰岛素抑制PGC-1α诱导的葡萄糖生成被胰岛素不敏感的FOXO1突变体逆转.
结论:
- 福克索1和PGC-1α形成了执行胰岛素调节的肝脏葡萄糖生成的关键综合体.
- 这种相互作用突出了控制葡萄糖生产的关键途径.
- 针对FOXO1-PGC-1alpha相互作用可能为代谢障碍提供治疗策略.
相关概念视频
Cell Specific Gene Expression
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...
Insulin Secretory Vesicles
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...
Hormones Regulating Blood Glucose
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...
Glucose Homeostasis: Regulation of Blood Glucose
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...
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
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 co-secreted in...
Insulin and C-peptide are co-secreted in...
Insulin: The Receptor and Signaling Pathways
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 this inhibition is released...

