Hyperinsulinemia alters insulin receptor presentation and internalization in brain microvascular endothelial cells.
Hyperinsulinemia alters insulin receptor presentation and internalization in brain microvascular endothelial cells.
复制标题
DOI：
10.1177/14791641221118626
复制
发表时间：
2022-07
影响因子：
2.4
通讯作者：
Sims-Robinson, Catrina
中科院分区：
文献类型：
--
作者：
Watson, Luke S.;Wilken-Resman, Brynna;Williams, Alexus;DiLucia, Stephanie;Sanchez, Guadalupe;McLeod, Taylor L.;Sims-Robinson, Catrina
胰岛素受体被内皮细胞内化以促进其生理过程;然而，尚不清楚高胰岛素血症对脑内皮细胞的影响。因此，本研究的目的是阐明高胰岛素血症通过磷酸化的变化对胰岛素受体内化的影响，以及蛋白酪氨酸磷酸酶1B（PTP 1B）的潜在影响。从高脂饮食喂养的小鼠中分离海马微血管，并评估胰岛素信号传导激活，这是一个已知与受体内化有关的过程。标记脑微血管内皮细胞中的表面胰岛素受体，以评估高胰岛素血症对刺激反应中受体内化的作用，有和没有PTP 1B拮抗剂，克拉明。我们的研究结果表明，在高脂饮食小鼠微血管中，胰岛素受体水平的增加与受体信号转导的减少相一致。接受高胰岛素血症治疗的细胞的胰岛素受体表现出朝向降低的IR-A mRNA表达的剪接变异，并表现出更高的膜定位比例。这与受体内化和信号传导关键位点的自磷酸化降低相对应。克拉拉明恢复了高胰岛素血症处理细胞中的信号传导和受体内化。总之，高胰岛素血症影响脑微血管内皮细胞胰岛素受体信号传导和内化，可能通过选择性剪接和增加PTP 1B的负反馈。
Insulin receptors are internalized by endothelial cells to facilitate their physiological processes; however, the impact of hyperinsulinemia in brain endothelial cells is not known. Thus, the aim of this study was to elucidate the impact hyperinsulinemia plays on insulin receptor internalization through changes in phosphorylation, as well as the potential impact of protein tyrosine phosphatase 1B (PTP1B). Hippocampal microvessels were isolated from high-fat diet fed mice and assessed for insulin signaling activation, a process known to be involved with receptor internalization. Surface insulin receptors in brain microvascular endothelial cells were labelled to assess the role hyperinsulinemia plays on receptor internalization in response to stimulation, with and without the PTP1B antagonist, Claramine. Our results indicated that insulin receptor levels increased in tandem with decreased receptor signaling in the high-fat diet mouse microvessels. Insulin receptors of cells subjected to hyperinsulinemic treatment demonstrate splice variation towards decreased IR-A mRNA expression and demonstrate a higher membrane-localized proportion. This corresponded with decreased autophosphorylation at sites critical for receptor internalization and signaling. Claramine restored signaling and receptor internalization in cells treated with hyperinsulinemia. In conclusion, hyperinsulinemia impacts brain microvascular endothelial cell insulin receptor signaling and internalization, likely via alternative splicing and increased negative feedback from PTP1B.
登录
查看更多内容
影响因子：
8.2
作者：
Gray SM;Aylor KW;Barrett EJ
通讯作者：
Barrett EJ
影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
6.3
作者：
Katakam, Prasad Venkateswera Gurunath;Domoki, Ferenc;Busija, David William
通讯作者：
Busija, David William
影响因子：
7.7
作者：
Janson, J;Laedtke, T;Butler, PC
通讯作者：
Butler, PC
影响因子：
8.2
作者：
CARPENTIER, JL
通讯作者：
CARPENTIER, JL