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

Guoli Chen, Ping Liu, Debbie C. Thurmond, Jeffrey Elmendorf

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)54-60
Number of pages7
JournalFEBS Letters
Volume534
Issue number1-3
DOIs
StatePublished - Jan 16 2003

Fingerprint

Glycosylation
Glucosamine
Qa-SNARE Proteins
Insulin Resistance
Cell membranes
Insulin
SNARE Proteins
Cell Membrane
Vesicle-Associated Membrane Protein 2
Membrane Fusion
Adipocytes
Carrier Proteins
Proteins
Fusion reactions
Association reactions
Membranes

Keywords

  • Glucosamine
  • GLUT4
  • Insulin resistance
  • Munc18c
  • SNARE protein

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Glucosamine-induced insulin resistance is coupled to O-linked glycosylation of Munc18c. / Chen, Guoli; Liu, Ping; Thurmond, Debbie C.; Elmendorf, Jeffrey.

In: FEBS Letters, Vol. 534, No. 1-3, 16.01.2003, p. 54-60.

Research output: Contribution to journalArticle

Chen, Guoli ; Liu, Ping ; Thurmond, Debbie C. ; Elmendorf, Jeffrey. / Glucosamine-induced insulin resistance is coupled to O-linked glycosylation of Munc18c. In: FEBS Letters. 2003 ; Vol. 534, No. 1-3. pp. 54-60.
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