星细胞胰岛素信号配对 脑摄取葡萄糖与营养的可用性
Cristina García-Cáceres1, Carmelo Quarta1, Luis Varela2
1Helmholtz Diabetes Center (HDC) & German Center for Diabetes Research (DZD), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Division of Metabolic Diseases, Technische Universität München, 80333 Munich, Germany.
Cell
|August 13, 2016
概括
星细胞中的胰岛素信号调节大脑的葡萄糖感应和新陈代谢. 在这些细胞中切除胰岛素受体会损害血糖控制和穿越血脑屏障的运输.
科学领域:
- 神经内分泌学
- 代谢调节
- 星球细胞生物学
背景情况:
- 星细胞在大脑功能和能量平衡中起着至关重要的作用.
- 大脑中的胰岛素信号影响葡萄糖代谢和神经元活动.
- 天体细胞胰岛素信号在下丘脑葡萄糖感应中的具体作用尚不清楚.
研究的目的:
- 研究星细胞胰岛素信号在下丘脑葡萄糖传感调节中的作用.
- 确定星细胞胰岛素受体如何影响全身葡萄糖代谢.
- 阐明星细胞通过血脑屏障控制葡萄糖运输的机制.
主要方法:
- 在小鼠体内表达状纤维酸蛋白 (GFAP) 细胞和表达谷氨酸酸转运体 (GLAST) 细胞中的胰岛素受体 (IR) 的产后切除.
- 对下丘脑天体细胞形态,线粒体功能和神经回路连接性的评估.
- 测量葡萄糖诱导的前皮质皮质神经元 (POMC) 的激活.
- 在GFAP- IR淘汰赛 (KO) 小鼠中进行体内正子发射断层扫描和脑脊液葡萄糖监测.
主要成果:
- 消去星系红细胞改变了星系细胞形态,线粒体功能和下丘脑电路连接性.
- 观察到葡萄糖诱导POMC神经元的激活减少,以及对葡萄糖可用性的生理反应受损.
- 绝杀星细胞IRs对直接中枢神经系统葡萄糖水平变化的反应没有影响,这表明它在血脑屏障葡萄糖运输中起作用.
- 在体内研究证实GFAP- IRKO小鼠的血脑屏障对葡萄糖的吸收受损.
结论:
- 在下丘脑星球细胞内的胰岛素信号对于共同调节中枢神经系统的葡萄糖感应至关重要.
- 通过通过血脑屏障调节葡萄糖吸收来控制全身葡萄糖代谢.
- 这些发现凸显了星细胞作为脑体葡萄糖沟通的关键媒介.
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