Metformin as an activator of AMP-activated protein kinase. Known and new mechanisms of action

Abstract

Metformin, known in the medical community as the drug of first choice for type 2 diabetes mellitus, belongs to the group of biguanides and has proven to be an effective treatment in clinical practice. Our knowledge of the pharmacodynamic properties of metformin has long been limited to the following well-known mechanisms: a decrease in hyperglycemia due to an increase in peripheral insulin sensitivity, glucose utilization by cells, inhibition of hepatic gluconeogenesis, an increase in the capacity of all types of membrane glucose transporters, activation of fibrinolysis, and a decrease in the levels of atherogenic lipoproteins. Recent studies show that the range of positive pleiotropic effects of metformin is not limited to the above, and that the molecular mechanisms of its action are more complex than previously thought. This article presents a less known, but equally important action of metformin, in particular, its anti-oncogenic, antiviral, and anti-aging effects. In our study, we highlight that the activation of 5’-adenosine monophosphate-activated protein kinase (AMPK) should be considered as the primary mechanism of action through which almost all beneficial effects are achieved. In the light of recent scientific advances in metformin pharmacology, together with the pathogenetic uncertainty of the term «biguanide», it seems fair and reasonable to apply a more relevant definition to the drugn, namely «AMPK activator».