Hexosamine flux, the O-GlcNAc modification, and the development of insulin resistance in adipocytes.
Excess flux through the hexosamine biosynthesis pathway in adipocytes is a fundamental cause of "glucose toxicity" and the development of insulin resistance that leads to type II diabetes. Adipose tissue-specific elevation in hexosamine flux in animal models recapitulates whole-body insulin-resistant phenotypes, and increased hexosamine flux in adipocyte cell culture models impairs insulin-stimulated glucose uptake. Many studies have been devoted to unveiling the molecular mechanisms in adipocytes in response to excess hexosamine flux-mediated insulin resistance. As a major downstream event consuming and incorporating the final product of the hexosamine biosynthesis pathway, dynamic and inducible O-GlcNAc modification is emerging as a modulator of insulin sensitivity in adipocytes. Given that O-GlcNAc is implicated in both insulin-mediated signal transduction and transcriptional events essential for adipocytokine secretion, direct functional studies to pinpoint the roles of O-GlcNAc in the development of insulin resistance via excess flux through hexosamine biosynthesis pathway are needed.
Complex Carbohydrate Research Center and Department of Biochemistry and Molecular Biology, University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
Chin Fen
CF
Teo
Edith E
EE
Wollaston-Hayden
Lance
L
Wells
D000117:Acetylglucosamine / Q000378:metabolism*; D017667:Adipocytes / Q000502:physiology*; D000818:Animals; D006031:Glycosylation; D006595:Hexosamines / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*
D006595:Hexosamines; D007328:Insulin; D000117:Acetylglucosamine