The Insulin-Like Growth Factor I Receptor Regulates Glucose Transport by Astrocytes
The Insulin-Like Growth Factor I Receptor Regulates Glucose Transport by Astrocytes
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DOI：
10.1002/glia.23035
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发表时间：
2016-11-01
期刊：
影响因子：
6.2
通讯作者：
Torres Aleman, Ignacio
中科院分区：
文献类型：
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作者：
Hernandez-Garzon, Edwin;Fernandez, Ana M.;Torres Aleman, Ignacio
先前的研究结果表明，减少大脑胰岛素样生长因子 I 受体 (IGF-IR) 的活性可促进充分的神经保护。我们现在研究了 IGF-IR 对大脑葡萄糖转运的可能作用，以解释其广泛的保护活性，因为能量可用性对于健康组织功能至关重要。使用 (18)FGlucose PET，我们发现小鼠体感皮层中 IGF-IR 的 shRNA 干扰显着增加了感觉刺激后的葡萄糖摄取。使用星形胶质细胞特异性染色的体内显微镜显示，在体感皮层注射 IGF-IR shRNA 后，与乱序注射侧的星形胶质细胞相比，星形胶质细胞的葡萄糖摄取量增加更大。此外，星形胶质细胞中 IGF-IR 被敲低的小鼠在感觉刺激后表现出体感皮层的葡萄糖摄取增加。对潜在机制的分析表明，IGF-IR 通过与支架蛋白 GIPC 和多货物转运蛋白 LRP1 相互作用的机制与星形胶质细胞中主要的促进性葡萄糖转运蛋白 GLUT1（GLUT1）相互作用，以将 GLUT1 保留在细胞内。这些发现表明 IGF-IR 通过抑制星形胶质细胞 GLUT1 活性而成为脑葡萄糖代谢的关键调节剂。
Previous findings indicate that reducing brain insulin-like growth factor I receptor (IGF-IR) activity promotes ample neuroprotection. We now examined a possible action of IGF-IR on brain glucose transport to explain its wide protective activity, as energy availability is crucial for healthy tissue function. Using (18)FGlucose PET we found that shRNA interference of IGF-IR in mouse somatosensory cortex significantly increased glucose uptake upon sensory stimulation. In vivo microscopy using astrocyte specific staining showed that after IGF-IR shRNA injection in somatosensory cortex, astrocytes displayed greater increases in glucose uptake as compared to astrocytes in the scramble-injected side. Further, mice with the IGF-IR knock down in astrocytes showed increased glucose uptake in somatosensory cortex upon sensory stimulation. Analysis of underlying mechanisms indicated that IGF-IR interacts with glucose transporter 1 (GLUT1), the main facilitative glucose transporter in astrocytes, through a mechanism involving interactions with the scaffolding protein GIPC and the multicargo transporter LRP1 to retain GLUT1 inside the cell. These findings identify IGF-IR as a key modulator of brain glucose metabolism through its inhibitory action on astrocytic GLUT1 activity.