PIK3R1 and Insulin resistance: In addition, the improvement of antipsychotic-induced insulin resistance by calcitriol was blocked in the presence of PI3K inhibitor in our in vitro experiments, further supporting the functional involvement of Pik3r1. Mice lacking both Pik3r1 and Pik3r2 in the skeletal muscles exhibit severely impaired PI3K signalling and insulin resistance25.