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高血糖会增加 SCO-spondin 和 Wnt5a 分泌到脑脊液中，从而调节室管膜细胞的跳动和葡萄糖感应。

Hyperglycemia increases SCO-spondin and Wnt5a secretion into the cerebrospinal fluid to regulate ependymal cell beating and glucose sensing.

机构信息

Laboratory of Neurobiology and Stem Cells, NeuroCellT, Department of Cellular Biology, Faculty of Biological Sciences, University of Concepcion, Concepcion, Chile.

Center for Advanced Microscopy CMA BIO BIO, University of Concepcion, Concepcion, Chile.

出版信息

PLoS Biol. 2023 Sep 21;21(9):e3002308. doi: 10.1371/journal.pbio.3002308. eCollection 2023 Sep.

DOI:10.1371/journal.pbio.3002308
PMID:37733692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10513282/
Abstract

Hyperglycemia increases glucose concentrations in the cerebrospinal fluid (CSF), activating glucose-sensing mechanisms and feeding behavior in the hypothalamus. Here, we discuss how hyperglycemia temporarily modifies ependymal cell ciliary beating to increase hypothalamic glucose sensing. A high level of glucose in the rat CSF stimulates glucose transporter 2 (GLUT2)-positive subcommissural organ (SCO) cells to release SCO-spondin into the dorsal third ventricle. Genetic inactivation of mice GLUT2 decreases hyperglycemia-induced SCO-spondin secretion. In addition, SCO cells secrete Wnt5a-positive vesicles; thus, Wnt5a and SCO-spondin are found at the apex of dorsal ependymal cilia to regulate ciliary beating. Frizzled-2 and ROR2 receptors, as well as specific proteoglycans, such as glypican/testican (essential for the interaction of Wnt5a with its receptors) and Cx43 coupling, were also analyzed in ependymal cells. Finally, we propose that the SCO-spondin/Wnt5a/Frizzled-2/Cx43 axis in ependymal cells regulates ciliary beating, a cyclic and adaptive signaling mechanism to control glucose sensing.

摘要

高血糖会增加脑脊液（CSF）中的葡萄糖浓度，激活下丘脑的葡萄糖感应机制和进食行为。在这里，我们讨论了高血糖如何暂时改变室管膜细胞纤毛的摆动，从而增加下丘脑的葡萄糖感应。大鼠 CSF 中的高葡萄糖水平会刺激 GLUT2 阳性的终末下器（SCO）细胞将 SCO-粘连蛋白释放到第三脑室背侧。小鼠 GLUT2 的基因失活会减少高血糖诱导的 SCO-粘连蛋白分泌。此外，SCO 细胞还分泌 Wnt5a 阳性囊泡；因此，Wnt5a 和 SCO-粘连蛋白位于背侧室管膜纤毛的顶端，以调节纤毛的摆动。我们还分析了 Frizzled-2 和 ROR2 受体以及特定的蛋白聚糖，如聚糖/测试聚糖（Wnt5a 与其受体相互作用所必需的）和 Cx43 偶联，在室管膜细胞中的作用。最后，我们提出 SCO-粘连蛋白/Wnt5a/Frizzled-2/Cx43 轴在室管膜细胞中调节纤毛的摆动，这是一种控制葡萄糖感应的周期性和适应性信号机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/1b0f2dd7ee39/pbio.3002308.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/e0e08b834695/pbio.3002308.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/8fc9f89ddf44/pbio.3002308.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/1bf59cf76e07/pbio.3002308.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/a6175ad143dc/pbio.3002308.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/10ccb82209dd/pbio.3002308.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/5f64bf317dae/pbio.3002308.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/43ef504569b4/pbio.3002308.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/16c3aa3c1f08/pbio.3002308.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/d7dacb026a7b/pbio.3002308.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/1b0f2dd7ee39/pbio.3002308.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/e0e08b834695/pbio.3002308.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/8fc9f89ddf44/pbio.3002308.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/1bf59cf76e07/pbio.3002308.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/a6175ad143dc/pbio.3002308.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/10ccb82209dd/pbio.3002308.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/5f64bf317dae/pbio.3002308.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/43ef504569b4/pbio.3002308.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/16c3aa3c1f08/pbio.3002308.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/d7dacb026a7b/pbio.3002308.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be44/10513282/1b0f2dd7ee39/pbio.3002308.g010.jpg

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