The PKGIα–Rac1 pathway is a novel regulator of insulin‐dependent glucose uptake in cultured rat podocytes,Journal of Cellular Physiology

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The PKGIα–Rac1 pathway is a novel regulator of insulin‐dependent glucose uptake in cultured rat podocytes
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-11-26 , DOI: 10.1002/jcp.30188
Irena Audzeyenka _{1,

2} , Dorota Rogacka _{1,

2} , Patrycja Rachubik ₁ , Marlena Typiak ₁ , Michał Rychłowski ₃ , Stefan Angielski ₁ , Agnieszka Piwkowska _{1,

2}

Affiliation

Insulin plays a major role in regulating glucose homeostasis in podocytes. Protein kinase G type Iα (PKGIα) plays an important role in regulating glucose uptake in these cells. Rac1 signaling plays an essential role in the reorganization of the actin cytoskeleton and is also essential for insulin‐stimulated glucose transport. The experiments were conducted using primary rat podocytes. We performed western blot analysis, evaluated small GTPases activity assays, measured radioactive glucose uptake, and performed immunofluorescence imaging to analyze the role of PKGIα‐Rac1 signaling in regulating podocyte function. We also utilized a small‐interfering RNA‐mediated approach to determine the role of PKGIα and Rac1 in regulating glucose uptake in podocytes. The present study investigated the influence of the PKGI pathway on the insulin‐dependent regulation of activity and cellular localization of small guanosine triphosphatases in podocytes. We found that the PKGIα‐dependent activation of Rac1 signaling induced activation of the PAK/cofilin pathway and increased insulin‐mediated glucose uptake in podocytes. The downregulation of PKGIα or Rac1 expression abolished this effect. Rac1 silencing prevented actin remodeling and GLUT4 translocation close to the cell membrane. These data provide evidence that PKGIα‐dependent activation of the Rac1 signaling pathways is a novel regulator of insulin‐mediated glucose uptake in cultured rat podocytes.

中文翻译：

PKGIα-Rac1 通路是培养大鼠足细胞中胰岛素依赖性葡萄糖摄取的新型调节剂

胰岛素在调节足细胞葡萄糖稳态中起着重要作用。 Iα 型蛋白激酶 G (PKGIα) 在调节这些细胞的葡萄糖摄取中发挥着重要作用。 Rac1 信号传导在肌动蛋白细胞骨架的重组中发挥着重要作用，对于胰岛素刺激的葡萄糖转运也至关重要。使用原代大鼠足细胞进行实验。我们进行了蛋白质印迹分析，评估了小 GTP 酶活性测定，测量了放射性葡萄糖摄取，并进行了免疫荧光成像，以分析 PKGIα-Rac1 信号传导在调节足细胞功能中的作用。我们还利用小干扰 RNA 介导的方法来确定 PKGIα 和 Rac1 在调节足细胞葡萄糖摄取中的作用。本研究调查了 PKGI 通路对足细胞中小鸟苷三磷酸酶活性和细胞定位的胰岛素依赖性调节的影响。我们发现，Rac1 信号传导的 PKGIα 依赖性激活诱导了 PAK/cofilin 通路的激活，并增加了足细胞中胰岛素介导的葡萄糖摄取。 PKGIα 或 Rac1 表达的下调消除了这种效应。 Rac1 沉默阻止肌动蛋白重塑和 GLUT4 易位靠近细胞膜。这些数据证明，Rac1 信号通路的 PKGIα 依赖性激活是培养大鼠足细胞中胰岛素介导的葡萄糖摄取的新型调节剂。

更新日期：2020-11-26

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