INS and Insulin resistance: Ceramide is mainly involved in the development of insulin resistance from two aspects: ceramide signal stimulates the binding of PKCζ and AKT, making AKT unable to bind phosphatidylinositol (3,4,5) -triphosphate (PIP3), thereby inhibiting insulin signaling [190]; on the other hand, ceramide activates protein phosphatase 2A (PP2A) and phosphorylates it, thereby impairing AKT [191].