相关实验视频

Updated: Jul 7, 2025

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy

Live Images of GLUT4 Protein Trafficking in Mouse Primary Hypothalamic Neurons Using Deconvolution Microscopy

Published on: December 7, 2017

托克斯3缺乏通过通过FoxO1抑制肝脏葡萄糖生成减轻高血糖症

Congcong Liu¹, Yuanwen Zheng², Shourui Hu¹

¹State Key Laboratory of Reproductive Medicine and Offspring Health, Shandong University, Jinan, Shandong 250012, China; Center for Reproductive Medicine, Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China.

Metabolism: clinical and experimental

|December 25, 2023

概括

托克斯3驱动肝脏过度生产葡萄糖,导致2型糖尿病的高血糖. 向TOX3可能为控制血糖水平提供了一种新的方法.

科学领域:

分子内分泌学分子内分泌学
代谢疾病代谢疾病
转录条例转录条例转录条例

背景情况:

过度的肝脏葡萄糖生产是导致2型糖尿病 (T2D) 高血糖的关键因素.
控制肝脏葡萄糖生产的调节机制尚未完全理解.
TOX3,一种高流动性组蛋白质,被确定为肝脏葡萄糖生产的显著转录调节器.

研究的目的:

研究TOX3在调节肝脏葡萄糖生产中的作用及其对高血糖的贡献.
阐明TOX3影响葡萄糖代谢的分子机制.
评估在T2D中准TOX3的治疗潜力.

主要方法:

产生Tox3-过度表达和淘汰赛小鼠模型.
转录和ChIP测序用于识别TOX3目标.
操纵FoxO1 (静音和抑制剂) 以评估其作用.
在人肝样本中分析TOX3表达.
在饮食诱导的肥胖小鼠中对Tox3的基因操纵.

主要成果:

肝脏TOX3过度表达增加了葡萄糖生成,导致高血糖和胰岛素抵抗.
肝细胞特异性TOX3淘汰会减少葡萄糖生成,改善胰岛素敏感性.
TOX3直接结合并激活FoxO1促销器,确定FoxO1作为一个关键的下游目标.
通过FoxO1沉默,消除了TOX3引起的高血糖症.
人类肝脏TOX3表达与血糖相关,但在T2D中被高葡萄糖抑制.
在糖尿病小鼠中,Tox3缺乏保护和改善了高血糖症.

结论:

通过激活肝脏FoxO1转录,TOX3驱动了过度的葡萄糖生成.
在2型糖尿病中,TOX3代表了管理高血糖的潜在治疗标.

关键词:

在FoxO1中,FoxO1是指FoxO1的类型.葡萄糖的产生和生成.过高血糖症的发生.在TOX3中使用TOX3.2 型糖尿病 2 型糖尿病

更多相关视频

Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes

Measurement of Fatty Acid β-Oxidation in a Suspension of Freshly Isolated Mouse Hepatocytes

Published on: September 9, 2021

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Hyperinsulinemic-euglycemic Clamps in Conscious, Unrestrained Mice

Published on: November 16, 2011

相关概念视频

Hypoglycemia and Glucagon

Hypoglycemia and Glucagon

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...

Hormones Regulating Blood Glucose

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...

Overview of Carbohydrate Metabolism

Overview of Carbohydrate Metabolism

Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to living cells. The most important carbohydrate is glucose, which can be broken down via glycolysis to enter into the Krebs cycle and eventually lead to the production of ATP through oxidative phosphorylation.
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...

Feedback Loops

Feedback Loops

In most cases, excessive hormone production is prevented by negative feedback—a loop that starts with a stimulus inducing the release of a particular substance, like a hormone, to maintain a certain level before triggering a signal that results in a decrease in further release of the hormone.

Glucose Homeostasis: Regulation of Blood Glucose

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...

Glucose Transporters

Glucose Transporters

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: