TNF and Hyperglycemia: In particular, one major intracellular target of hyperglycemia and oxidative stress is the transcription factor NF-κB. NF-κB can be activated by a wide array of exogenous and endogenous stimuli including hyperglycemia, elevated FFA, ROS, tumor necrosis factor-α, interleukin-1β, other proinflammatory cytokines, AGE-binding RAGE, and p38 MAPK.