Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane

Bayasgalan Jambaldorj, Eri Terada, Toshio Hosaka, Yuka Kishuku, Yukiko Tomioka, Kaori Iwashima, Yohko Hirata, Kiyoshi Teshigawara, Chung Thi Kim Le, Tadahiko Nakagawa, Nagakatsu Harada, Tohru Sakai, Hiroshi Sakaue, Toshio Matsumoto, Makoto Funaki, Akira Takahashi, Yutaka Nakaya

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)197-204
Number of pages8
JournalJournal of Medical Investigation
Volume60
Issue number3-4
DOIs
Publication statusPublished - Nov 8 2013
Externally publishedYes

Keywords

  • Cysteine string protein 1
  • GLUT4
  • SNARE
  • VAMP2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Jambaldorj, B., Terada, E., Hosaka, T., Kishuku, Y., Tomioka, Y., Iwashima, K., Hirata, Y., Teshigawara, K., Le, C. T. K., Nakagawa, T., Harada, N., Sakai, T., Sakaue, H., Matsumoto, T., Funaki, M., Takahashi, A., & Nakaya, Y. (2013). Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane. Journal of Medical Investigation, 60(3-4), 197-204. https://doi.org/10.2152/jmi.60.197