AMPK activators: mechanisms of action and physiological activities

AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, which coordinates metabolic pathways and thus balances nutrient supply with energy demand. Because of the favorable physiological outcomes of AMPK activation on metabolism, AMPK has been considered to be an important therapeutic target for controlling human diseases including metabolic syndrome and cancer. Thus, activators of AMPK may have potential as novel therapeutics for these diseases. In this review, we provide a comprehensive summary of both indirect and direct AMPK activators and their modes of action in relation to the structure of AMPK. We discuss the functional differences among isoform-specific AMPK complexes and their significance regarding the development of novel AMPK activators and the potential for combining different AMPK activators in the treatment of human disease. An enzyme with a key role in metabolism could offer a target for drugs to treat obesity, type 2 diabetes and cancer. The enzyme AMPK (AMP-activated protein kinase) is crucial for regulating energy and metabolism in cells, and is thought to be important in protecting against several diseases. Joohun Ha and colleagues at Kyung Hee University, Seoul, have reviewed the research into agents designed to activate AMPK to assess their feasibility as drugs. The researchers suggest that AMPK activators are potentially useful for the treatment of conditions such as obesity, type 2 diabetes and cancer. Combining different AMPK activators in different clinical contexts might provide optimal treatment. They conclude that more research is needed to determine the precise mechanisms of action of AMPK activators and thereby optimize treatment strategies.