Abstract
In this minireview, we will highlight work in the last 30 years that has clearly demonstrated that the O-GlcNAc modification is nutrient-responsive and plays multiple roles in metabolic regulation of signaling and gene expression. Further, we will examine recent studies that have investigated the impact of O-GlcNAc in a variety of glucose- and insulin-responsive tissues and the roles attributed to O-GlcNAc in the induction of insulin resistance and glucose toxicity, the hallmarks of type II diabetes mellitus. We will also summarize potential causal roles for the O-GlcNAc modification in complications associated with diabetes.