Although there are many unknowns and anomalies in our knowledge of insulin-signalling pathways, the mechanisms of glucose uptake, and the metabolic processes involved in insulin resistance, these loopholes could be addressed if researchers were to focus more on key factors such as IRS1, its phosphorylation, the translocation of GLUT4, and the roles of cytokines such as TNFα, not forgetting how PPARγ, JNK, and IKKβ contribute to insulin resistance. This evidence concerns the gene IRS1 and Insulin resistance.