• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

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.

Pubmed ID: 16377570

Authors

  • Ohtsubo K
  • Takamatsu S
  • Minowa MT
  • Yoshida A
  • Takeuchi M
  • Marth JD

Journal

Cell

Publication Data

December 29, 2005

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK48247
  • Agency: NIGMS NIH HHS, Id: GM62116

Mesh Terms

  • Animals
  • Cells, Cultured
  • Diabetes Mellitus, Type 2
  • Diet
  • Dietary Fats
  • Glucose Transporter Type 2
  • Glycosylation
  • Insulin
  • Insulin-Secreting Cells
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • N-Acetylglucosaminyltransferases
  • Up-Regulation