The inhibition of C16 ceramide synthesis has emerged as an effective strategy to improve glucose and lipid metabolism abnormalities in various diseases, such as diabetes, nonalcoholic steatohepatitis, cardiovascular disease, etc. The present results suggest that CGA restrained glucagon response by reducing the concentration of C16 ceramides, which preserved the Akt phosphorylation, thereby inhibiting the hepatic glucose production. The gene discussed is GCG; the disease is diabetes mellitus.