Cross-talk between GlcNAcylation and phosphorylation: Roles in insulin resistance and glucose toxicity

Ronald J. Copeland, John W. Bullen, Gerald Warren Hart

Research output: Contribution to journalArticlepeer-review

Abstract

O-linked β-N-acetylglucosamine (O-GlcNAc) is a dynamic posttranslational modification that, analogous to phosphorylation, cycles on and off serine and/or threonine hydroxyl groups. Cycling of O-GlcNAc is regulated by the concerted actions of O-GlcNAc transferase and O-GlcNAcase. GlcNAcylation is a nutrient/stress-sensitive modification that regulates proteins involved in a wide array of biological processes, including transcription, signaling, and metabolism. GlcNAcylation is involved in the etiology of glucose toxicity and chronic hyperglycemia-induced insulin resistance, a major hallmark of type 2 diabetes. Several reports demonstrate a strong positive correlation between GlcNAcylation and the development of insulin resistance. However, recent studies suggest that inhibiting GlcNAcylation does not prevent hyperglycemia-induced insulin resistance, suggesting that other mechanisms must also be involved. To date, proteomic analyses have identified more than 600 GlcNAcylated proteins in diverse functional classes. However, O-GlcNAc sites have been mapped on only a small percentage (

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume295
Issue number1
DOIs
StatePublished - Jul 2008

Keywords

  • β-N-acetylglucosaminidase
  • Diabetes
  • Hexosamine biosynthesis
  • O-linked β-N- acetylglucosamine transferase
  • O-linked β-N-acetylglucosamine

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Biochemistry

Fingerprint Dive into the research topics of 'Cross-talk between GlcNAcylation and phosphorylation: Roles in insulin resistance and glucose toxicity'. Together they form a unique fingerprint.

Cite this