| First Author | Ohtsubo K | Year | 2005 |
| Journal | Cell | Volume | 123 |
| Issue | 7 | Pages | 1307-21 |
| PubMed ID | 16377570 | Mgi Jnum | J:117542 |
| Mgi Id | MGI:3696712 | Doi | 10.1016/j.cell.2005.09.041 |
| Citation | Ohtsubo K, et al. (2005) Dietary and genetic control of glucose transporter 2 glycosylation promotes insulin secretion in suppressing diabetes. Cell 123(7):1307-21 |
| abstractText | Pancreatic beta cell-surface expression of glucose transporter 2 (Glut-2) is essential for glucose-stimulated insulin secretion, thereby controlling blood glucose homeostasis in response to dietary intake. We show that the murine GlcNAcT-IVa glycosyltransferase is required for Glut-2 residency on the beta cell surface by constructing a cell-type- and glycoprotein-specific N-glycan ligand for pancreatic lectin receptors. Loss of GlcNAcT-IVa, or the addition of glycan-ligand mimetics, attenuates Glut-2 cell-surface half-life, provoking endocytosis with redistribution into endosomes and lysosomes. The ensuing impairment of glucose-stimulated insulin secretion leads to metabolic dysfunction diagnostic of type 2 diabetes. Remarkably, the induction of diabetes by chronic ingestion of a high-fat diet is associated with reduced GlcNAcT-IV expression and attenuated Glut-2 glycosylation coincident with Glut-2 endocytosis. We infer that beta cell glucose-transporter glycosylation mediates a link between diet and insulin production that typically suppresses the pathogenesis of type 2 diabetes. |
