Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.
Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability.
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DOI：
10.1016/j.cell.2016.07.028
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发表时间：
2016-08-11
期刊：
影响因子：
64.5
通讯作者：
Tschöp MH
中科院分区：
文献类型：
--
作者：
García-Cáceres C;Quarta C;Varela L;Gao Y;Gruber T;Legutko B;Jastroch M;Johansson P;Ninkovic J;Yi CX;Le Thuc O;Szigeti-Buck K;Cai W;Meyer CW;Pfluger PT;Fernandez AM;Luquet S;Woods SC;Torres-Alemán I;Kahn CR;Götz M;Horvath TL;Tschöp MH
我们报告星形细胞胰岛素信号共同调节下丘脑葡萄糖传感和全身葡萄糖代谢。神经胶质纤维酸性蛋白（GFAP）表达细胞中胰岛素受体（IR）的出生后消融影响了下丘脑星形胶质细胞的形态、线粒体功能和回路连接。因此，星形细胞IR消融减少了葡萄糖诱导的下丘脑阿片黑皮质素原（POMC）神经元的激活，并损害了对葡萄糖可用性变化的生理反应。下丘脑特异性敲除星形细胞 IR 以及通过靶向表达谷氨酸天冬氨酸转运蛋白 (GLAST) 的细胞进行的出生后消融复制了此类改变。缺乏星形胶质细胞IR的小鼠对中枢神经系统葡萄糖水平改变的正常反应表明其在葡萄糖跨血脑屏障（BBB）转运中发挥作用。使用正电子发射断层扫描以及脑脊液中的葡萄糖监测在 GFAP-IR KO 小鼠体内证实了这一点。我们得出的结论是，下丘脑星形胶质细胞中的胰岛素信号通过调节血脑屏障的葡萄糖摄取共同控制中枢神经系统葡萄糖传感和全身葡萄糖代谢。下丘脑星形胶质细胞的胰岛素感应共同调节脑葡萄糖感应和全身葡萄糖代谢。
We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in Glial fibrillary acidic protein (GFAP)-expressing cells affected hypothalamic astrocyte morphology, mitochondrial function and circuit connectivity. Accordingly, astrocytic IR ablation reduced glucose-induced activation of hypothalamic Pro-opio-melanocortin (POMC) neurons and impaired physiological responses to changes in glucose availability. Hypothalamus-specific knock out of astrocytic IRs as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells replicated such alterations. A normal response to altering CNS glucose levels in mice lacking astrocytic IRs indicated a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice using positron emission tomography as well as glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. Insulin sensing by hypothalamic astrocytes co-regulates brain glucose sensing and systemic glucose metabolism.
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影响因子：
56.9
作者：
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通讯作者：
Horvath, TL
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