INS and type 2 diabetes mellitus: It was demonstrated that patients with diabetes type 2 show elevated plasma levels of the Zn2+-dependent secretory ASM (Gorska et al., 2003) and incubation of rat hepatocytes with ceramide or ASM resulted in the phosphorylation of insulin receptor substrate (IRS-1) leading to blocked insulin signaling and thereby insulin resistance (Herschkovitz et al., 2007).