Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane.
Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane.
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DOI：
10.2152/jmi.60.197
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发表时间：
2013
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通讯作者：
Bayasgalan Jambaldorj;E. Terada;T. Hosaka;Yuka Kishuku;Y. Tomioka;Kaori Iwashima;Yohko Hirata;K. Teshigawara;Chung Thi Kim Le;Tadahiko Nakagawa;N. Harada;T. Sakai;H. Sakaue;Toshio Matsumoto;M. Funaki;A. Takahashi;Y. Nakaya
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作者：
Bayasgalan Jambaldorj;E. Terada;T. Hosaka;Yuka Kishuku;Y. Tomioka;Kaori Iwashima;Yohko Hirata;K. Teshigawara;Chung Thi Kim Le;Tadahiko Nakagawa;N. Harada;T. Sakai;H. Sakaue;Toshio Matsumoto;M. Funaki;A. Takahashi;Y. Nakaya
胰岛素刺激葡萄糖转运蛋白 4 (GLUT4) 囊泡从其细胞内储存位点募集到质膜。半胱氨酸串蛋白 1 (CSP1) 是一种 SNARE 结合蛋白，参与神经递质的囊泡运输和其他胞吐过程。在这项研究中，我们研究了 CSP1 在 3T3-L1 脂肪细胞中胰岛素依赖性 GLUT4 募集中的作用。野生型 CSP1 的过度表达导致胰岛素刺激的葡萄糖摄取减弱，质膜中 GLUT4 含量没有任何变化，而是通过阻断 VAMP2 与突触融合蛋白 4 的结合来抑制对接。相反，CSP1 的敲低增强了胰岛素刺激的葡萄糖摄取。在高水平棕榈酸酯和长期胰岛素暴露引起的胰岛素抵抗状态下，3T3-L1脂肪细胞中CSP1的mRNA和蛋白表达升高。总而言之，这项研究的结果表明，CSP1 通过中断 GLUT4 囊泡与质膜的对接来参与胰岛素抵抗。
Insulin stimulates glucose transporter 4 (GLUT4) vesicle recruitment from its intracellular storage site to the plasma membrane. Cysteine string protein 1 (CSP1) is a SNARE-binding protein involved in the vesicular trafficking of neurotransmitters and other exocytic processes. In this study, we investigated the involvement of CSP1 in insulin-dependent GLUT4 recruitment in 3T3-L1 adipocytes. Over-expression of wild-type CSP1 led to attenuated insulin-stimulated glucose uptake without any change in GLUT4 content in the plasma membrane, rather it inhibits docking by blocking the association of VAMP2 with syntaxin 4. In contrast, knockdown of CSP1 enhanced insulin-stimulated glucose uptake. The mRNA and protein expression of CSP1 was elevated in 3T3-L1 adipocytes in insulin resistant states caused by high levels of palmitate and chronic insulin exposure. Taken together, the results of this study suggest that CSP1 is involved in insulin resistance by interrupting GLUT4 vesicle docking with the plasma membrane.