Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells.
Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells.
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DOI：
10.3390/ijms241914670
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发表时间：
2023-09-28
影响因子：
5.6
通讯作者：
Sims-Robinson C
中科院分区：
文献类型：
--
作者：
DiLucia SG;Kendrick BJ;Sims-Robinson C
脑组织的充分灌注是保持最佳脑健康所必需的，其取决于脑内皮细胞内的胰岛素信号传导。适当的胰岛素信号传导依赖于与胰岛素受体结合的胰岛素的调节内化，这一过程通过未知的机制被高胰岛素血症破坏。因此，本研究的目的是表征高胰岛素血症对参与脑血流和胰岛素受体内化至脑内皮细胞的分子靶点的调节的影响。在高胰岛素血症脑内皮细胞中评估了与脑血流和胰岛素受体内化相关的分子靶点的磷酸化。还在胞吞作用阻断的情况下检查了胰岛素受体摄取到细胞中。我们的数据表明，高胰岛素血症损害内皮型一氧化氮合酶的激活。这些数据与网格蛋白介导的胰岛素受体内吞作用和关键内化效应物磷酸化失调的损害相对应。我们的结论是，高胰岛素血症改变参与网格蛋白介导的内吞作用的分子靶点的磷酸化，破坏通过胰岛素受体的信号传导，并阻碍脑内皮细胞的血流调节能力。
Adequate perfusion of cerebral tissues, which is necessary for the preservation of optimal brain health, depends on insulin signaling within brain endothelial cells. Proper insulin signaling relies on the regulated internalization of insulin bound to the insulin receptor, a process which is disrupted by hyperinsulinemia via an unknown mechanism. Thus, the goal of this study was to characterize the impact of hyperinsulinemia on the regulation of molecular targets involved in cerebral blood flow and insulin receptor internalization into brain endothelial cells. The phosphorylation of molecular targets associated with cerebral blood flow and insulin receptor internalization was assessed in hyperinsulinemic brain endothelial cells. Insulin receptor uptake into cells was also examined in the setting of endocytosis blockade. Our data demonstrate that hyperinsulinemia impairs the activation of endothelial nitric oxide synthase. These data correspond with an impairment in clathrin-mediated endocytosis of the insulin receptor and dysregulated phosphorylation of key internalization effectors. We conclude that hyperinsulinemia alters the phosphorylation of molecular targets involved in clathrin-mediated endocytosis, disrupts signaling through the insulin receptor, and hinders the capacity for blood flow regulation by brain endothelial cells.
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影响因子：
8.2
作者：
Gray SM;Aylor KW;Barrett EJ
通讯作者：
Barrett EJ
影响因子：
16.6
作者：
Choi, Eunhee;Kikuchi, Sotaro;Yu, Hongtao
通讯作者：
Yu, Hongtao
影响因子：
3.4
作者：
Guo, Shuohan;Zhang, Xiaohan;Kim, Kyeong-Man
通讯作者：
Kim, Kyeong-Man
DOI：
10.1152/ajpendo.00350.2016
发表时间：
2018-10-01
影响因子：
5.1
作者：
Hersom, Maria;Helms, Hans C.;Brodin, Birger
通讯作者：
Brodin, Birger
影响因子：
56.9
作者：
KING, GL;JOHNSON, SM
通讯作者：
JOHNSON, SM