New insights: A role for O-GlcNAcylation in diabetic complications

Crit Rev Biochem Mol Biol. 2016 May-Jun;51(3):150-61. doi: 10.3109/10409238.2015.1135102. Epub 2016 Jan 24.


Diabetes is a debilitating metabolic disease that is riddled with complications that can cause blindness, renal failure, nerve damage, and cardiovascular disease. Poor glycemic control is thought to be a key initiator in the progression of diabetic complications. Hyperglycemia has been shown to increase flux through the hexosamine biosynthetic pathway (HBP) to initiate many of the toxic effects of glucose. The major endpoint of the HBP is the formation of uridine diphosphate β-D-N-acetylglucosamine (UDP-GlcNAc), the donor for protein O-GlcNAcylation, and complex extracellular glycosylation. O-GlcNAcylation is a dynamic nutrient sensitive post-translational modification that is characterized by the addition of single β-D-N-acetylglucosamine to the serine and/or threonine residues of almost every functional class of protein. O-GlcNAc is extremely abundant and cycles on and off proteins by the concerted action of a transferase and a hydrolase. O-GlcNAc serves as a nutrient/stress sensor regulating several processes, such as signaling, transcription, cytoskeletal dynamics, and cell division. Altered O-GlcNAc signaling is directly involved in the pathogenesis of diabetes and new insights are revealing the importance of O-GlcNAc in diabetic complications. The goal of this review is to summarize O-GlcNAcylation, to present the current evidence for the role of O-GlcNAc in diabetic complications, and discuss conclusions and future directions for research on O-GlcNAc in the progression of diabetic complications.

Keywords: Cardiovascular disease; O-GlcNAc; diabetes; diabetic nephropathy; diabetic retinopathy; glucose toxicity; hexosamine biosynthetic pathway; hyperglycemia.

Publication types

  • Review

MeSH terms

  • Acetylglucosamine / metabolism*
  • Animals
  • Diabetes Complications / metabolism*
  • Diabetes Mellitus / metabolism*
  • Glycosylation
  • Hexosamines / metabolism
  • Humans
  • Protein Processing, Post-Translational


  • Hexosamines
  • Acetylglucosamine