INS and Hyperglycemia: As the O-GlcNAc modification has been detected on a number of proteins involved in the insulin signaling cascade, such as Akt (Park et al., 2005), IRS-1 (Ball et al., 2006), and FoxO1 (Housley et al., 2008), elevated O-GlcNAc levels have the potential to be a molecular mechanism that links hyperglycemia to insulin resistance.