Metformina e AMPK: Um Antigo Fármaco e Uma Nova Enzima no Contexto da Síndrome Metabólica perspectivas

ABSTRACT Metformin and AMPK: An Old Drug and a New Enzyme in the Con-text of Metabolic Syndrome.Metformin is one of the most commonly prescribed oral antidiabetic agents worldwide. However, its mechanism of action remains unknown. The Diabe-tes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the inci-dence of Diabetes Mellitus type 2 (DM2). A possible biochemical connection between both therapies may be the AMP-activated protein kinase (AMPK). This enzyme was originally described as a sensor of cellular energy status, being activated in exercise. On the other hand, several experimental evidenc-es indicate that AMPK may be an important target of metformin action. Thispaper discusses various ways for AMPK regulation, suggesting a possible mechanism for its activation by metformin that involves the production of reactive nitrogen species. AMPK activation determines a wide variety of physiological effects, including enhanced glucose uptake by skeletal muscle and enhanced lipid catabolism. Thus, it may be a key player not only in the prevention and treatment of DM2, but also in the development of new treat-ments for obesity and the metabolic syndrome. The finding of AMPK activa-tion by metformin draws attention to this enzyme as an important pharmacological target.