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

Autor: Kaori Iwashima, Tadahiko Nakagawa, Chung Thi Kim Le, Bayasgalan Jambaldorj, Makoto Funaki, Akira Takahashi, Hiroshi Sakaue, Yuka Kishuku, Toshio Matsumoto, Tohru Sakai, Toshio Hosaka, Nagakatsu Harada, Kiyoshi Teshigawara, Yutaka Nakaya, Yohko Hirata, Eri Terada, Yukiko Tomioka
Rok vydání: 2013
Předmět:
Zdroj: The journal of medical investigation : JMI. 60(3-4)
ISSN: 1349-6867
Popis: 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.
Databáze: OpenAIRE