Glucokinase (GCK), arginase-1 (Arg-1), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) are molecules closely associated with hepatic gluconeogenesis and play crucial roles in regulating glucose metabolism, insulin resistance, and metabolic diseases such as diabetes mellitus. This evidence concerns the gene GCK and metabolic disease.