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: |
Vesicle-Associated Membrane Protein 2
medicine.medical_treatment Glucose uptake Vesicle docking Biology General Biochemistry Genetics and Molecular Biology Mice Insulin resistance Downregulation and upregulation 3T3-L1 Cells medicine Adipocytes Animals RNA Messenger Glucose Transporter Type 4 VAMP2 Qa-SNARE Proteins Insulin Cell Membrane Glucose transporter Membrane Proteins General Medicine HSP40 Heat-Shock Proteins medicine.disease Cell biology Up-Regulation SNARE cysteine string protein 1 Gene Knockdown Techniques biology.protein Insulin Resistance GLUT4 |
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 |
Externí odkaz: |