MAPK8 and Hyperglycemia: Additionally, diabetic peripheral neuropathy is caused by the effects of chronic exposure to hyperglycemia, which promote glycotoxic stress, inducing increased oxidative stress with increased ROS; dysfunction of the antioxidant system; activation of the JNK, AP-1, PKC, NFκB, and MAPK; the additional formation of polyols and glycosamines; AGE favoring the transcription of genes encoding TGF-β, IL-1, IL-6, and TNF-α; and induced nitric oxide (iNOS).