N-Glycosylation modulates the membrane sub-domain distribution and activity of glucose transporter 2 in pancreatic beta cells

Biochem Biophys Res Commun. 2013 May 3;434(2):346-51. doi: 10.1016/j.bbrc.2013.03.076. Epub 2013 Mar 30.


The glucose transporter isoform, GLUT2, -mediated glucose sensing is essential for maintaining normal glucose-stimulated insulin secretion in pancreatic beta cells. We previously reported that GnT-IVa glycosyltransferase is required for the production of an N-glycan structure that acts as a ligand for galectins to form the glycan-galectin lattice that maintains the stable cell surface expression of GLUT2, and cellular glucose transport activity, although the functional relevance of the N-glycosylation of GLUT2 to its membrane sub-domain distribution is not fully understood. In the present study, we demonstrated that disruption of the GLUT2 N-glycan-galectin lattice by the genetic inactivation of GnT-IVa, or by treatment of pancreatic beta cells with competitive glycan mimetics, induced the re-distribution of GLUT2 into the lipid-raft microdomain. This subsequently resulted in the binding of Stomatin to GLUT2 and an attenuation of cellular glucose transport activity. Moreover, disruption of the lipid-raft microdomain by treatment with methyl-β-cyclodextrin caused the GLUT2 to be released from lipid-rafts and reactivation of the cellular glucose transport activity in GnT-IVa deficient beta cells. These results indicate that the membrane sub-domain distribution of GLUT2 is associated with the glucose transport activity of beta cells, in which the GnT-IVa-dependent formation of the N-glycan-galectin lattice plays an important role. This provides a novel pathophysiological insight into the mechanism of beta cell failure in the pathogenesis of type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Blood Proteins / metabolism
  • Galectins / metabolism
  • Glucose / metabolism
  • Glucose / pharmacology
  • Glucose Transporter Type 2 / metabolism*
  • Glycosylation
  • Immunoprecipitation
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism*
  • Membrane Microdomains / metabolism*
  • Membrane Proteins / metabolism
  • Mice
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism
  • Polysaccharides / metabolism
  • Primary Cell Culture
  • Protein Binding
  • beta-Cyclodextrins / pharmacology


  • Blood Proteins
  • Epb7.2 protein, mouse
  • Galectins
  • Glucose Transporter Type 2
  • Membrane Proteins
  • Polysaccharides
  • Slc2a2 protein, mouse
  • beta-Cyclodextrins
  • methyl-beta-cyclodextrin
  • N-Acetylglucosaminyltransferases
  • alpha-1,3-mannosylglycoprotein beta-1,4-N-acetylglucosaminyltransferase
  • Glucose