Glucosamine‐induced insulin resistance is coupled to O‐linked glycosylation of Munc18c

FEBS Letters

Chen, Guoli¹  Elmendorf, Jeffrey S.¹  Liu, Ping¹  Thurmond, Debbie C.¹ 

[1] Departments of Cellular and Integrative Physiology, and Biochemistry and Molecular Biology, Indiana University School of Medicine, Center for Diabetes Research, Indianapolis, IN 46202-5120, USA

关键词: GLUT4;    Glucosamine;    Insulin resistance;    Munc18c;    SNARE protein;    GLUT4;    insulin-responsive glucose transporter;    SNARE;    soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor;    VAMP;    vesicle-associated membrane protein;    PI3K;    phosphatidylinositol 3-kinase;    GFAT;    glutamine:fructose-6-phosphate amidotransferase;    GlcNAc;    N-acetylglucosamine;    EGFP;    enhanced green fluorescent protein;    DMEM;    Dulbecco's modified Eagle's medium;    FBS;    fetal bovine serum;    SNAP23;    synaptosome-associated protein of 23 kDa;    IR;    insulin receptor;   

DOI  :  10.1016/S0014-5793(02)03774-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Evidence suggests that glucosamine inhibits distal components regulating insulin-stimulated GLUT4 translocation to the plasma membrane. Here we assessed whether key membrane docking and fusion events were targeted. Consistent with a plasma membrane-localized effect, 3T3-L1 adipocytes exposed to glucosamine displayed an increase in cell-surface O-linked glycosylation and a simultaneously impaired mobilization of GLUT4 by insulin. Analysis of syntaxin 4 and SNAP23, plasma membrane-localized target receptor proteins (t-SNAREs) for the GLUT4 vesicle, showed that they were not cell-surface targets of O-linked glycosylation. However, the syntaxin 4 binding protein, Munc18c, was targeted by O-linked glycosylation. This occurred concomitantly with a block in insulin-stimulated association of syntaxin 4 with its cognate GLUT4 vesicle receptor protein (v-SNARE), VAMP2. In conclusion, our data suggest that the mechanism by which glucosamine inhibits insulin-stimulated GLUT4 translocation involves modification of Munc18c.

【 授权许可】

Unknown