炎症通过IKKβ-XBP1s相互作用改善葡萄糖平衡
Junli Liu1, Dorina Ibi1, Koji Taniguchi2
1Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02130, USA.
Cell
|November 5, 2016
概括
涉及IκB激酶β (IKKβ) 的炎症对肝脏葡萄糖平衡产生积极的调节. 通过减少ER压力,提高肥胖小鼠的IKKβ提高了胰岛素敏感性和葡萄糖稳定性.
科学领域:
- 代谢和内分泌学
- 分子生物学
- 细胞信号传输
背景情况:
- 与肥胖相关的炎症与2型糖尿病的发展有关.
- IκB激酶β (IKKβ) 是炎症途径中的关键激酶,通常与胰岛素抵抗有关.
- 在肝脏葡萄糖代谢中IKKβ介导的炎症的确切作用尚不完全理解.
研究的目的:
- 调查IKKβ介导的炎症在肝脏葡萄糖平衡中的作用.
- 确定调节IKKβ活动是否会影响肥胖患者的胰岛素敏感性和葡萄糖调节.
主要方法:
- 使用了三种不同的实验策略,特别是在肥胖小鼠的肝脏中提升IKKβ活性.
- 评估了增强IKKβ活性对X-Box结合蛋白1 (XBP1s) 结合活性的影响.
- 监测了内质网膜 (ER) 的压力水平,并评估了胰岛素敏感性和葡萄糖平衡.
主要成果:
- 增加的IKKβ活动导致XBP1s在肝脏中的活性增强.
- 增加的IKKβ活动导致ER压力降低.
- 肥胖小鼠的胰岛素敏感性和葡萄糖稳定性显著改善.
结论:
- 与普遍认为的相反,IKKβ介导的肝炎起到葡萄糖平衡的积极调节作用.
- 这些有益作用的关键机制是XBP1s的IKKβ酸化.
- 针对肝脏IKKβ活性可能为治疗胰岛素抵抗和2型糖尿病提供一种新的治疗策略.
相关概念视频
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
2.9K
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...
2.9K
Hormones Regulating Blood Glucose
8.0K
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...
8.0K
Glucose Homeostasis: Regulation of Blood Glucose
4.9K
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...
4.9K
Insulin Secretory Vesicles
7.2K
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...
7.2K
Cell Specific Gene Expression
16.8K
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...
16.8K
Dipeptidyl Peptidase 4 Inhibitors
845
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
845


