Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.
Ras-related C3 botulinum toxin substrate 1 (RAC1) regulates glucose-stimulated insulin secretion via modulation of F-actin.
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DOI：
10.1007/s00125-013-2849-5
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发表时间：
2013-05
期刊：
影响因子：
8.2
通讯作者：
Kido, Y.
中科院分区：
文献类型：
--
作者：
Asahara, S.;Shibutani, Y.;Teruyama, K.;Inoue, H. Y.;Kawada, Y.;Etoh, H.;Matsuda, T.;Kimura-Koyanagi, M.;Hashimoto, N.;Sakahara, M.;Fujimoto, W.;Takahashi, H.;Ueda, S.;Hosooka, T.;Satoh, T.;Inoue, H.;Matsumoto, M.;Aiba, A.;Kasuga, M.;Kido, Y.
小G蛋白ras相关的C3肉毒毒素底物1(RAC1)在哺乳动物细胞中发挥着多种作用，如调节细胞骨架组织、细胞黏附、迁移和形态变化。本研究旨在探讨RAC1消融对胰岛β细胞功能的影响。从胰岛β细胞特异的Rac1基因敲除小鼠(−/−)分离的胰岛和经小干扰RNA处理的Rac1基因敲除的INS-1胰岛素瘤细胞用于研究胰岛β细胞的胰岛素分泌和细胞骨架组织。−/−小鼠表现出葡萄糖刺激的胰岛素分泌减少，而胰岛形态没有明显差异。从小鼠身上分离出来的胰岛对高血糖水平的反应减弱了胰岛素的分泌。在Rac1基因敲除的INS-1细胞中，胰岛素分泌也因高糖水平而减少，这与Betarac1−/−小鼠的表型一致。即使在高糖水平下，RAC1基因敲除的INS-1细胞仍保持完整的F-肌动蛋白，它抑制胰岛素颗粒的募集，从而抑制胰岛素的分泌。在缺乏RAC1的胰岛细胞中，F-肌动蛋白作为胰岛素颗粒的屏障，减少了葡萄糖刺激的胰岛素分泌。这篇文章的在线版本(doi：10.1007/s00125.0132849-5)包含经同行审查但未经编辑的补充材料，授权用户可获得这些材料。
The small G-protein ras-related C3 botulinum toxin substrate 1 (RAC1) plays various roles in mammalian cells, such as in the regulation of cytoskeletal organisation, cell adhesion, migration and morphological changes. The present study examines the effects of RAC1 ablation on pancreatic beta cell function. Isolated islets from pancreatic beta cell-specific Rac1-knockout (betaRac1 −/−) mice and RAC1 knockdown INS-1 insulinoma cells treated with small interfering RNA were used to investigate insulin secretion and cytoskeletal organisation in pancreatic beta cells. BetaRac1 −/− mice showed decreased glucose-stimulated insulin secretion, while there were no apparent differences in islet morphology. Isolated islets from the mice had blunted insulin secretion in response to high glucose levels. In RAC1 knockdown INS-1 cells, insulin secretion was also decreased in response to high glucose levels, consistent with the phenotype of betaRac1 −/− mice. Even under high glucose levels, RAC1 knockdown INS-1 cells remained intact with F-actin, which inhibits the recruitment of the insulin granules, resulting in an inhibition of insulin secretion. In RAC1-deficient pancreatic beta cells, F-actin acts as a barrier for insulin granules and reduces glucose-stimulated insulin secretion. The online version of this article (doi:10.1007/s00125-013-2849-5) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
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影响因子：
4.1
作者：
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通讯作者：
TYHURST, M
影响因子：
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作者：
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