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

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  • Jambaldorj Bayasgalan
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Terada Eri
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Hosaka Toshio
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Kishuku Yuka
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Tomioka Yukiko
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Iwashima Kaori
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Hirata Yohko
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Teshigawara Kiyoshi
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Thi Kim Le Chung
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Nakagawa Tadahiko
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Harada Nagakatsu
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Sakai Tohru
    Department of Public Health and Applied Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Sakaue Hiroshi
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Matsumoto Toshio
    Department of Medicine and Bioregulatory Sciences, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Funaki Makoto
    Clinical Research Center for Diabetes, Tokushima University Hospital
  • Takahashi Akira
    Department of Preventive Environment and Nutrition, Institute of Health Biosciences, the University of Tokushima Graduate School
  • Nakaya Yutaka
    Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School

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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. J. Med. Invest. 60: 197-204, August, 2013

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