PDK4 and Insulin resistance: Moreover, the combined impact of G1 treatment and a high-fat diet on pyruvate metabolism, as well as the regulation of crucial gluconeogenesis enzymes such as pyruvate dehydrogenase kinase 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 2 (GLUT2), expedites the elevation of blood glucose and the progression of insulin resistance.