Hepatic Targets to Control Blood Glucose and Potentially Aid in the Treatment of Diabetes

Maintaining glucose homeostasis is extremely important to remain in good health and prevent disease. This homeostasis is achieved via the regulation of hepatic metabolic pathways like gluconeogenesis and glycogenesis by insulin, which is expressed during high blood glucose. Insulin is responsible for facilitating the uptake of glucose into other tissues from the blood, as well as signaling whether to stimulate or slow glucose metabolism in the liver. Hyperglycemia is one of the main effects of diabetes, a disease characterized by the body’s inability to produce or respond to insulin. Without insulin, hepatic glucose output continues and blood glucose accumulates, causing health complications that arise with the development of diabetes. Aside from the regulation of hepatic glucose metabolism by insulin, recent research has pointed towards targeting enzymes within these metabolic pathways in the liver to lower blood glucose. In this review, mechanisms to target two enzymes in hepatic gluconeogenesis and glycogenesis will be explored: fructose 1,6-bisphosphatase and glucokinase, respectively. Additionally, existent and potential drugs with these targeting mechanisms will be introduced, highlighting their effects on blood glucose regulation in diabetic models. The ability to target enzymes involved in hepatic glucose metabolism to reduce hyperglycemia provides insight into methods and treatments alternative to insulin that have potential to be used for the treatment of diabetes.