Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10759528 | Biochemical and Biophysical Research Communications | 2013 | 6 Pages |
Abstract
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.
Keywords
DTSSPN-acetylglucosaminyltransferaseGNTKRHHEPES2-NBDGDSPHBSSGLUTpKaMβCDPBS4-(2-hydroxyethyl)-1-piperazineethanesulfonic acidDMSOAdenosine tri-phosphateATPGlucose transporterDimethyl sulfoxidePhosphate buffered salinemethyl-β-cyclodextrinHank’s balanced salt solutionprotein kinase Aglucose transporter 2Glycosylation
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Authors
Kazuaki Ohtsubo, Shinji Takamatsu, Congxiao Gao, Hiroaki Korekane, Tsutomu M. Kurosawa, Naoyuki Taniguchi,