INS and Insulin resistance: This is because O-GlcNAc modifications of a number of insulin signaling intermediates have been shown to cause insulin resistance,74–76 and emerging evidence suggests that O-GlcNAc modification of immune signaling intermediates modify protein activity during cellular activation and differentiation.77 For instance, O-GlcNAc modification of the NF-κB subunit c-Rel is required for its DNA binding activity and subsequent cytokine expression in activated T cells.78 The inhibition of O-GlcNAc modification in this context is sufficient to repress IL-2 and IFNG expression following TCR stimulation.