| Summary: | O-GlcNAcylation is a posttranslational modification ruled by the activity of a single pair of enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). These two enzymes carry out the dynamic cycling of O-GlcNAcylation on a wide range of cytosolic, nuclear, and mitochondrial proteins in a nutrient- and stress-responsive manner. To maintain proper glucose homeostasis, a precise mechanism to sense blood glucose levels is required, to adapt cell physiology to fluctuations in nutrient intake to maintain glycemia within a narrow range. Disruptions in glucose homeostasis generates metabolic syndrome and type 2 diabetes. In this review we will discuss and summarize emerging findings that points O-GlcNAcylation as a hub in the control of systemic glucose homeostasis, and its involvement in the generation of insulin resistance and type 2 diabetes.
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