Title : Dietary and genetic control of
glucose transporter 2 glycosylation promotes
insulin secretion in suppressing diabetes
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