INS and Insulin resistance: However, very few peripheral insulin can access the brain through the BBB in T2D due to the hyperinsulinemia and brain insulin resistance (Arnold et al. 2018; El Khoury et al. 2014; Freude et al. 2005), which was also proven in our animal experiments, as subcutaneous insulin injection failed to remarkably increase the insulin level in CSF (Figs. 2B, 3B).