Targeting hepatic glucose metabolism in the treatment of type 2 diabetes

Although the liver has a key role in maintaining blood glucose homeostasis, few existing type 2 diabetes therapies directly target this organ. Here, Puigserveret al. provide an overview of the molecular mechanisms controlling hepatic gluconeogenesis and glycogen storage, focusing on emerging strategies to target hepatic glucose metabolism for the treatment of diabetes. Type 2 diabetes mellitus is characterized by the dysregulation of glucose homeostasis, resulting in hyperglycaemia. Although current diabetes treatments have exhibited some success in lowering blood glucose levels, their effect is not always sustained and their use may be associated with undesirable side effects, such as hypoglycaemia. Novel antidiabetic drugs, which may be used in combination with existing therapies, are therefore needed. The potential of specifically targeting the liver to normalize blood glucose levels has not been fully exploited. Here, we review the molecular mechanisms controlling hepatic gluconeogenesis and glycogen storage, and assess the prospect of therapeutically targeting associated pathways to treat type 2 diabetes.