Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
Ohtsubo K,Takamatsu S,Minowa MT,Yoshida A,Takeuchi M,Marth JDdoi
10.1016/j.cell.2005.09.041subject
Has Abstractpub_date
2005-12-29 00:00:00pages
1307-21issue
7eissn
0092-8674issn
1097-4172pii
S0092-8674(05)01171-2journal_volume
123pub_type
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