Inducing insulin resistance in such manipulated cell line models is often complex or unachievable20To gain a deeper understanding of the molecular mechanisms underlying insulin resistance, we performed a multi-layered MS-based proteomics investigation in a HepG2 liver cell line model with endogenous IR expression and knock-out of the insulin-like growth factor 1 receptor (IGF1R KO). The gene discussed is IGF1R; the disease is Insulin resistance.