TNF and Hyperglycemia: Importantly, several transcription factors, such as NF-κB (37, 38) and Sp1 (Figure 2C) (39), can be directly/indirectly activated by hyperglycemia-induced O-GlcNAcylation leading to the up-regulation of pro-inflammatory factors, including TGF-β, TNF-α and PAI-1, and down-regulation of SERCA2a leading to abnormal intracellular Ca2+ transient (38–40).