| First Author | Ohtsubo K | Year | 2013 |
| Journal | Biochem Biophys Res Commun | Volume | 434 |
| Issue | 2 | Pages | 346-51 |
| PubMed ID | 23548572 | Mgi Jnum | J:201282 |
| Mgi Id | MGI:5512927 | Doi | 10.1016/j.bbrc.2013.03.076 |
| Citation | Ohtsubo K, et al. (2013) N-Glycosylation modulates the membrane sub-domain distribution and activity of glucose transporter 2 in pancreatic beta cells. Biochem Biophys Res Commun 434(2):346-51 |
| abstractText | 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-beta-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. |
