INS and type 2 diabetes mellitus: Preliminary studies demonstrated that treatment with chemical inhibitors of ceramide biosynthesis enhances insulin sensitivity, and treatment with peroxisome proliferator-activated receptor (PPAR) agonists, which improve insulin responsiveness and reduce oxidative stress [83, 148-150], decrease hepatic ceramide generation, serum ceramide levels, cognitive impairment, and neurodegeneration in models of DIO with T2DM and steatohepatitis [151].