O-GlcNAc modification of transcription factors, glucose sensing and glucotoxicity

Trends Endocrinol Metab. 2008 Dec;19(10):380-9. doi: 10.1016/j.tem.2008.09.001. Epub 2008 Oct 17.


Regulation of proteins by O-GlcNAc modification is becoming a major area of research. This reversible modification depends on glucose concentrations and, therefore, constitutes a powerful mechanism to regulate protein activities according to glucose availability. Its importance in glucose-dependent gene transcription is underlined by its role in pancreatic insulin biosynthesis (through PDX-1 and NeuroD1 O-GlcNAc modifications) and leptin synthesis in adipose tissue (through Sp1 O-GlcNAc modification). Moreover, in chronic hyperglycaemia, O-GlcNAc modifications of Sp1, p53 and NFkappaB participate in glucotoxicity, resulting in cardiovascular and renal alterations. The recent discovery by two independent groups that FoxO1 is regulated by O-GlcNAc modification provides a potential mechanism by which hyperglycaemia promotes gluconeogenesis and worsening of glucose intolerance, opening new research perspectives in the field.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylglucosamine / metabolism*
  • Animals
  • Glucose / adverse effects*
  • Glucose / metabolism*
  • Humans
  • Models, Biological
  • Protein Processing, Post-Translational / physiology*
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology


  • Transcription Factors
  • Glucose
  • Acetylglucosamine