Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.
Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.
复制标题
脑周细胞衍生的可溶性因子增强 GT1-7 下丘脑神经元的胰岛素敏感性。
DOI：
10.1016/j.bbrc.2015.01.016
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kataoka Y.
中科院分区：
文献类型：
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作者：
Takahashi H;Takata F;Matsumoto J;Machida T;Yamauchi A;Dohgu S;Kataoka Y.
下丘脑中的胰岛素信号在食物摄取和血糖稳态中起着重要作用。下丘脑神经功能由神经胶质细胞调节；这些细胞形成一个广泛的网络，连接神经元和脑血管系统，称为神经血管单位(NVU)。脑周细胞是血脑屏障的内皮周围附属结构，是NVU的组成部分。然而，周细胞和神经元之间的相互作用在很大程度上还没有被探索。在这里，我们研究脑周细胞是否会影响下丘脑神经元胰岛素信号。我们的免疫组织化学观察表明，小鼠下丘脑中存在周细胞，表现出血小板衍生生长因子受体β(周细胞标记物)和层粘连蛋白(基底膜标记物)的免疫反应。然后，我们将小鼠下丘脑神经细胞系GT1-7暴露于从大鼠脑周细胞原代培养中获得的条件培养液中。周细胞条件培养液(PCM)，而不是星形胶质细胞或主动脉平滑肌细胞条件培养液，以浓度依赖的方式增加胰岛素刺激的GT1-7细胞Akt的磷酸化。PCM还增强了胰岛素刺激的胰岛素受体β的酪氨酸磷酸化，而不改变其在胞浆或质膜部分的表达或定位。这些结果表明，在NVU的生理条件下，周细胞而不是星形胶质细胞通过释放可溶性因子来增加下丘脑神经元的胰岛素敏感性。
Insulin signaling in the hypothalamus plays an important role in food intake and glucose homeostasis. Hypothalamic neuronal functions are modulated by glial cells; these form an extensive network connecting the neurons and cerebral vasculature, known as the neurovascular unit (NVU). Brain pericytes are periendothelial accessory structures of the blood–brain barrier and integral members of the NVU. However, the interaction between pericytes and neurons is largely unexplored. Here, we investigate whether brain pericytes could affect hypothalamic neuronal insulin signaling. Our immunohistochemical observations demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting immunoreactivity of platelet-derived growth factor receptor β (a pericyte marker), and laminin, a basal lamina marker. We then exposed a murine hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor β without changing its expression or localization in cytosolic or plasma membrane fractions. These results suggest that pericytes, rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by releasing soluble factors under physiological conditions in the NVU.