Protein Modification by u0001-N-Acetyl Glucosamine (O-GlcNAc) in Insulin Signaling and Insulin Resistance

摘要

Abstract: An enzymatic posttranslational modification of proteins at serine or threonine residue by u0001-N-acetyl nglucosamine (GlcNAcylation, also known as O-GlcNAc modification), a product of hexosamine biosynthetic pathway n(HBP), has been emerging as a fundamental regulatory mechanism like protein phosphorylation. A significant surge in the ninformation in recent years due to technological advancement has implicated an important role for GlcNAcylation in a nwide variety of cellular processes including cell division, metabolism, signal transduction and transcription. Furthermore, nGlcNAcylation in proteins has been found to be intimately associated with phosphorylation which is one of the most ndiverse regulatory mechanisms in the biological system. Therefore, it is likely that altered protein GlcNAcylation may nunderlie etiology of various diseases including type 2 diabetes. Emerging evidence strongly indicates a role for nGlcNAcylation in the development of insulin resistance, a hallmark of type 2 diabetes. Recent findings on protein nGlcNAcylation, especially in relation to insulin signaling and insulin resistance have regenerated an immense interest in nthis field; which was first reported in early nineties. Here we summarize recent development in this area along with nunanswered questions and future direction at the end. Some of the recently patented technologies in relation to nGlcNAcylation are also summarized in this review. Further investigations in this area are timely and of critical importance nwith continuous increase in the incidence of type 2 diabetes and diabetes associated complications worldwide. A better nunderstanding of the underlying mechanisms may provide new opportunities for the prevention and treatment of type 2 ndiabetes.