MAPK8 and obesity due to melanocortin 4 receptor deficiency: Specifically, oxidative stress contributes to insulin resistance through an “oxidative-inflammatory cascade (OIC).” Glucose, obesity, and oxidative stress reduce intracellular antioxidant defense mechanisms while activating inflammatory responses from transcription factors and kinases, such as c-Jun N-terminal kinase (JNK), protein kinase C (PKC), and inhibitor of kappa B kinase-β (IKKβ) (25).