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

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 inve...

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Bibliographic Details
Published in:	The Journal of Medical Investigation Vol. 60; no. 3.4; pp. 197 - 204
Main Authors:	Jambaldorj, Bayasgalan, Terada, Eri, Hosaka, Toshio, Kishuku, Yuka, Tomioka, Yukiko, Iwashima, Kaori, Hirata, Yohko, Teshigawara, Kiyoshi, Le, Chung Thi Kim, Nakagawa, Tadahiko, Harada, Nagakatsu, Sakai, Tohru, Sakaue, Hiroshi, Matsumoto, Toshio, Funaki, Makoto, Takahashi, Akira, Nakaya, Yutaka
Format:	Journal Article
Language:	English
Published:	Japan The University of Tokushima Faculty of Medicine 2013
Subjects:	3T3-L1 Cells Adipocytes - metabolism Animals Cell Membrane - metabolism cysteine string protein 1 Gene Knockdown Techniques Glucose Transporter Type 4 - metabolism GLUT4 HSP40 Heat-Shock Proteins - antagonists & inhibitors HSP40 Heat-Shock Proteins - genetics HSP40 Heat-Shock Proteins - metabolism Insulin Resistance - physiology Membrane Proteins - antagonists & inhibitors Membrane Proteins - genetics Membrane Proteins - metabolism Mice Qa-SNARE Proteins - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism SNARE Up-Regulation VAMP2 Vesicle-Associated Membrane Protein 2 - metabolism
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Summary:	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. J. Med. Invest. 60: 197-204, August, 2013
ISSN:	1343-1420 1349-6867
DOI:	10.2152/jmi.60.197