The mechanisms involved in the etiopathogenesis of insulin resistance related to obesity occur due to prereceptor, receptor, and/or postreceptor impairments, mainly to insulin receptor downregulation secondary to hyperinsulinemia (receptor) and inhibition of the intracellular cascades by several adiposity-related factors (e.g., impaired adipokines and/or cytokines secretion) (after receptor) [49]. The gene discussed is INSR; the disease is hyperinsulinism.