It has been shown that p31comet can inhibit INSR endocytosis by inhibiting the interaction of BUBR1 and INSR-bound MAD2, and liver-specific p31comet−/− mice exhibit reduced INSR levels and develop systemic insulin resistance, while Bubr1 deficiency delays INSR endocytosis and improves insulin sensitivity in mice29,44. This evidence concerns the gene INSR and Insulin resistance.