title: Metformin therapy in diabetes: the role of cardioprotection.
abstract: In patients with diabetes mellitus, the incidence of cardiovascular disease is increased, and the outcome following cardiovascular events is worse. The antihyperglycemic drug metformin appears to limit cardiovascular death in patients with type 2 diabetes. Indeed, preclinical studies have demonstrated that metformin limits (myocardial) ischemia and reperfusion injury, independent from its glucose-lowering effect. This cardioprotection is mediated by activation of the Reperfusion Injury Salvage Kinase (RISK) pathway, activation of AMPK and by an increased formation of adenosine. In addition, metformin can modulate several cardiovascular risk factors and reduces the development of heart failure in murine models. Consequently, treatment with metformin might potentially improve cardiovascular outcome in patients at risk for myocardial ischemia, even if these patients do not have diabetes. In the current paper, we focus on the direct cardioprotective actions of metformin and the mechanisms that underlie these effects.
authors: Department of Pharmacology-Toxicology 149, Radboud University Nijmegen Medical Center, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. S.elMessaoudi@cardio.umcn.nl
authors: Saloua
authors: S
authors: El Messaoudi
authors: Gerard A
authors: GA
authors: Rongen
authors: Niels P
authors: NP
authors: Riksen
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000209:etiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
chemical_list: D002316:Cardiotonic Agents; D007004:Hypoglycemic Agents; D008687:Metformin