Even though receptor endocytosis is the main negative regulator, Ser/Thr phosphorylation in response to insulin and other stimuli, including cytokines, free fatty acids, hyperglycemia, and subsequently oxidative stress, as well as mitochondrial dysfunction and endoplasmic reticulum (ER) stress, are also critical factors playing a role in the pathogenesis of insulin resistance [14]. The gene discussed is INS; the disease is Insulin resistance.