Premium
Glucosamine‐induced insulin resistance is coupled to O‐linked glycosylation of Munc18c
Author(s) -
Chen Guoli,
Liu Ping,
Thurmond Debbie C.,
Elmendorf Jeffrey S.
Publication year - 2003
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03774-2
Subject(s) - glut4 , glycosylation , snap23 , microbiology and biotechnology , insulin resistance , chemistry , insulin , membrane protein , biochemistry , biology , membrane , vesicle associated membrane protein 8 , endocrinology
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.