脂肪细胞PI3K通过脂克列的作用,将脂肪酸与快食时的基线胰岛素分泌联系起来
Barbara Becattini1, Angela Molinaro1, Marcus Henricsson1
1Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
Cell reports
|April 24, 2024
概括
脂肪组织的胰岛素信号,特别是PI3Kα和PI3Kβ,影响胰岛素分泌. 抑制脂肪细胞中的这种途径会触发"脂烯效应",增加自由脂肪酸并刺激禁食期间的胰岛素释放.
科学领域:
- 代谢信号传递是代谢信号传递.
- 内分泌学 在内分泌学.
- 脂肪组织生物学 脂肪组织生物学
背景情况:
- 胰岛素-PI3K信号传递对胰岛素分泌至关重要,但其在体内脂肪组织中的作用尚未完全理解.
- 研究胰岛素功能的反机制对于代谢健康至关重要.
- 脂肪细胞胰岛素信号对胰岛素分泌的影响需要进一步阐明.
研究的目的:
- 为了研究脂肪细胞胰岛素-PI3K信号在控制体内胰岛素分泌中的作用.
- 在脂肪细胞中确定PI3Kα和PI3Kβ之间的功能冗余.
- 描述一种新的反机制,将脂肪细胞的胰岛素信号与胰岛素分泌联系起来.
主要方法:
- 使用脂细胞特异性PI3Kα淘汰小鼠 (PI3KαAdQ).
- 在药理学研究中使用异形选择性PI3K抑制剂.
- 测量了脂肪细胞AKT酸化和血清自由脂肪酸 (FFA) 水平.
- 在禁食条件下评估体内胰岛素分泌.
主要成果:
- PI3Kα和PI3Kβ在脂肪细胞胰岛素信号传递中表现出功能冗余.
- 急性脂肪细胞选择性PI3K抑制会提高血清FFA,并强烈诱导胰岛素分泌 (脂克瑞效应).
- 阿迪波因克莱丁的作用发生在禁食期间,随着FFA的上升和葡萄糖的下降,这表明它调节脂解和基础胰岛素分泌,而不是主要是葡萄糖平衡.
结论:
- 脂肪细胞胰岛素-PI3K信号传递在调节胰岛素分泌中起着关键作用.
- 一个新的反循环,脂烯酸效应,将脂细胞脂解与胰岛素分泌联系起来.
- 这一途径主要通过FFA调节来控制禁食期间的基础胰岛素分泌.
关键词:
在 AKT AKT 里面.CP:新陈代谢过程中的新陈代谢在PI3K中,PI3K是指PI3K.糖尿病 糖尿病患者 糖尿病患者增长因素 增长因素 增长因素这种形形的形形.胰岛素的胰岛素胰岛素是什么胰岛素耐药性是一种胰岛素耐药性.胰岛素分泌的胰岛素分泌.在mTOROR中使用mTOR.肥胖 肥胖 肥胖 肥胖 肥胖 肥胖 肥胖 肥胖更多相关视频
相关概念视频
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
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion
1.2K
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...
1.2K
Insulin Secretory Vesicles
4.9K
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...
4.9K
Phosphoinositides and PIPs
8.5K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.5K
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
PI3K/mTOR/AKT Signaling Pathway
3.5K
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...
3.5K


