Dietary and Genetic Control of Glucose Transporter 2 Glycosylation Promotes Insulin Secretion in Suppressing Diabetes

Pancreatic β 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 β...

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Bibliographic Details
Published in:Cell 2005-12, Vol.123 (7), p.1307-1321
Main Authors: Ohtsubo, Kazuaki, Takamatsu, Shinji, Minowa, Mari T., Yoshida, Aruto, Takeuchi, Makoto, Marth, Jamey D.
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Diabetes Mellitus, Type 2 - enzymology
Diabetes Mellitus, Type 2 - genetics
Diabetes Mellitus, Type 2 - prevention & control
Diet
Dietary Fats - administration & dosage
Dietary Fats - pharmacology
Glucose Transporter Type 2 - genetics
Glucose Transporter Type 2 - metabolism
Glycosylation
Insulin - biosynthesis
Insulin - metabolism
Insulin Secretion
Insulin-Secreting Cells - chemistry
Mice
Mice, Inbred C57BL
Mice, Transgenic
N-Acetylglucosaminyltransferases - deficiency
N-Acetylglucosaminyltransferases - genetics
N-Acetylglucosaminyltransferases - metabolism
Up-Regulation
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Summary:Pancreatic β 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 β 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 β cell glucose-transporter glycosylation mediates a link between diet and insulin production that typically suppresses the pathogenesis of type 2 diabetes.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2005.09.041