Role of O-linked N-acetylglucosamine in the homeostasis of metabolic organs, and its potential links with diabetes and its complications

Recent studies using genetically manipulated mouse models have shown the pivotal role of O-linked N-acetylglucosamine modification (O-GlcNAcylation) in the metabolism of multiple organs. The molecular mechanism involves the sensing of glucose flux by the hexosamine biosynthesis pathway, which leads to the adjustment of cellular metabolism to protect against changes in the environment of each organ through O-GlcNAcylation. More recently, not only glucose, but also fluxes of amino acids and fatty acids have been reported to induce O-GlcNAcylation, affecting multiple cellular processes. In this review, we discuss how O-GlcNAcylation maintains homeostasis in organs that are affected by diabetes mellitus: skeletal muscle, adipose tissue, liver and pancreatic beta-cells. Furthermore, we discuss the importance of O-GlcNAcylation in the pathogenesis of diabetic complications. By elucidating the molecular mechanisms whereby cellular homeostasis is maintained, despite changes in metabolic flux, these studies might provide new targets for the treatment and prevention of diabetes and its complications.

Automated summary

Recent studies highlight the crucial role of O-GlcNAcylation in metabolic regulation of various organs, sensing changes in metabolic flux and modifying cellular metabolism for adaptation. Not only glucose, but also amino acids and fatty acids have been shown to induce O-GlcNAcylation. Understanding the molecular mechanisms of cellular homeostasis maintenance through O-GlcNAcylation may offer new targets for diabetes treatment and prevention.