title: Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane.
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.
authors.affiliation: Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School.
authors.forename: Bayasgalan
authors.initials: B
authors.lastname: Jambaldorj
authors.forename: Eri
authors.initials: E
authors.lastname: Terada
authors.forename: Toshio
authors.initials: T
authors.lastname: Hosaka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kishuku
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tomioka
authors.forename: Kaori
authors.initials: K
authors.lastname: Iwashima
authors.forename: Yohko
authors.initials: Y
authors.lastname: Hirata
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Teshigawara
authors.forename: Chung
authors.initials: C
authors.lastname: Thi Kim Le
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakaue
authors.forename: Toshio
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Funaki
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D055785:Gene Knockdown Techniques; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D050956:HSP40 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D050765:Qa-SNARE Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D051275:Glucose Transporter Type 4; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D012333:RNA, Messenger; C495693:Slc2a4 protein, mouse; D050988:Vesicle-Associated Membrane Protein 2; C088460:cysteine string protein; C494808:vesicle-associated membrane protein 2, mouse