[Metformin and AMPK: an old drug and a new enzyme in the context of metabolic syndrome].
Metformin is one of the most commonly prescribed oral antidiabetic agents worldwide. However, its mechanism of action remains unknown. The Diabetes Prevention Program Research Group studies have shown that metformin administration and lifestyle-intervention (diet and exercise) reduce the incidence 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 evidences indicate that AMPK may be an important target of metformin action. This paper 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 treatments for obesity and the metabolic syndrome. The finding of AMPK activation by metformin draws attention to this enzyme as an important pharmacological target.
Santomauro Júnior
Augusto Cézar
AC
Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Ugolini
Michelle Remião
MR
Santomauro
Ana Teresa
AT
Souto
Ricardo Peres do
RP
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control; D004032:Diet; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000201:enzymology* / Q000517:prevention & control; D008687:Metformin / Q000378:metabolism / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D055372:AMP-Activated Protein Kinases; D005947:Glucose