在MAD2-依赖性胰岛素受体内细胞结核中调节代谢平衡
Junhee Park1, Catherine Hall1, Brandon Hubbard2
1Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY.
Diabetes
|September 19, 2023
概括
破坏胰岛素受体 (IR) -MAD2相互作用会延迟从细胞中去除IR,延长胰岛素的作用,并影响葡萄糖和脂肪代谢. 这突显了细胞分裂蛋白在代谢调节中的作用.
科学领域:
- 细胞生物学 细胞生物学
- 代谢调节 代谢调节 代谢调节
- 内分泌学 在内分泌学.
背景情况:
- 胰岛素受体 (IR) 信号传递对葡萄糖平衡至关重要.
- 红外线内细胞酶减弱胰岛素信号传递,但其生理作用尚不清楚.
- 细胞分裂调节器MAD2,BUBR1和p31comet都与红外线内细胞分裂有关.
研究的目的:
- 研究IR-MAD2相互作用在胰岛素信号传递和代谢调节中的作用.
- 确定扰乱IR-MAD2相互作用对IR内细胞和胰岛素清除的影响.
- 阐明红外内细胞酶在维持能量平衡中的作用.
主要方法:
- 在小鼠中,IR-MAD2相互作用的遗传除.
- 对红外线内细胞分裂,胰岛素信号和葡萄糖代谢的分析.
- 血清脂肪酸度和肝脏脂肪积累的评估.
- 肝脏和脂肪组织的转录基因分析.
主要成果:
- 对IR-MAD2相互作用的遗传干扰延迟了IR内细胞形成,并延长了细胞表面的胰岛素作用.
- 这种干扰导致胰岛素清除受损,循环胰岛素和葡萄糖激素水平增加,葡萄糖代谢发生改变.
- 在禁食的雄性小鼠中观察到血清脂肪酸度增加和肝脏脂肪积累.
- 在肝脏和脂肪组织中发现了明显的代谢和转录基因变化.
结论:
- 这种IR-MAD2相互作用对于高效的IR内细胞和胰岛素清除至关重要.
- 细胞分裂调节器在调节胰岛素信号和代谢过程中发挥着重要作用.
- 红外内细胞分裂的破坏会影响系统能量恒温,突出显示其治疗意义.
相关概念视频
Insulin: The Receptor and Signaling Pathways
1.3K
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...
1.3K
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 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
PI3K/mTOR/AKT Signaling Pathway
3.6K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
3.6K
Hormones Regulating Blood Glucose
3.5K
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...
3.5K
Carbohydrate Metabolism
11.2K
Carbohydrates are polymers composed of molecules containing atoms of carbon, hydrogen and oxygen. One gram of carbohydrate can provide four kilo-calories of energy, which makes it the most efficient instant energy source.
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
Starch accounts for approximately 60% of the carbohydrates consumed by humans. Since amylase enzymes cannot function in the stomach's acidic environment, starch can only be digested in the mouth and small intestine. Simple sugars are found naturally in milk and fruits in...
11.2K


