Protein Modification by β-N-Acetyl Glucosamine (O-GlcNAc) in Insulin Signaling and Insulin Resistance
Sudharsana R. Ande and Suresh Mishra
Affiliation: Diabetes Research Group, University of Manitoba, 843 JBRC/715 McDermot Avenue, Winnipeg, MB R3E 3P4, Canada.
Keywords: Glucose, GlcNAc, GlcNAc transferase, GlcNAc amidase, GlcNAcylation, glycation, hexosamine biosynthetic pathway, insulin resistance, insulin signaling, phosphorylation, posttranslational modification, protein-protein interaction, type 2 diabetes, tyrosine phosphorylation
An enzymatic posttranslational modification of proteins at serine or threonine residue by β-N-acetyl glucosamine (GlcNAcylation, also known as O-GlcNAc modification), a product of hexosamine biosynthetic pathway (HBP), has been emerging as a fundamental regulatory mechanism like protein phosphorylation. A significant surge in the information in recent years due to technological advancement has implicated an important role for GlcNAcylation in a wide variety of cellular processes including cell division, metabolism, signal transduction and transcription. Furthermore, GlcNAcylation in proteins has been found to be intimately associated with phosphorylation which is one of the most diverse regulatory mechanisms in the biological system. Therefore, it is likely that altered protein GlcNAcylation may underlie etiology of various diseases including type 2 diabetes. Emerging evidence strongly indicates a role for GlcNAcylation in the development of insulin resistance, a hallmark of type 2 diabetes. Recent findings on protein GlcNAcylation, especially in relation to insulin signaling and insulin resistance have regenerated an immense interest in this field; which was first reported in early nineties. Here we summarize recent development in this area along with unanswered questions and future direction at the end. Some of the recently patented technologies in relation to GlcNAcylation are also summarized in this review. Further investigations in this area are timely and of critical importance with continuous increase in the incidence of type 2 diabetes and diabetes associated complications worldwide. A better understanding of the underlying mechanisms may provide new opportunities for the prevention and treatment of type 2 diabetes.
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