Metformin improves cardiac function in rats via activation of AMP‐activated protein kinase

1. Metformin is one of the most commonly used drugs for the treatment of Type 2 diabetes. Accumulating evidence suggests that metformin also has cardioprotective effects. In the present study, we investigated the cardioprotective effects of metformin and the mechanisms involved.

[1]  H. Bøtker,et al.  Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration. , 2008, Basic & clinical pharmacology & toxicology.

[2]  S. Jha,et al.  Acute Metformin Therapy Confers Cardioprotection Against Myocardial Infarction Via AMPK-eNOS–Mediated Signaling , 2008, Diabetes.

[3]  B. Viollet,et al.  Compound C inhibits hypoxic activation of HIF‐1 independent of AMPK , 2007, FEBS letters.

[4]  F. McAlister,et al.  Benefits and harms of antidiabetic agents in patients with diabetes and heart failure: systematic review , 2007, BMJ : British Medical Journal.

[5]  F. Gaskin,et al.  5′‐AMP‐activated protein kinase activation prevents postischemic leukocyte‐endothelial cell adhesive interactions: Role of nitric oxide , 2006, American journal of physiology. Heart and circulatory physiology.

[6]  J. Shyy,et al.  Statins Activate AMP-Activated Protein Kinase In Vitro and In Vivo , 2006, Circulation.

[7]  T. Garland,et al.  AMP-Activated Protein Kinase Is Involved in Endothelial NO Synthase Activation in Response to Shear Stress , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[8]  B. Viollet,et al.  Activation of the AMP-activated kinase by antidiabetes drug metformin stimulates nitric oxide synthesis in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. , 2006, Diabetes.

[9]  S. Kihara,et al.  Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2–dependent mechanisms , 2005, Nature Medicine.

[10]  T. Funahashi,et al.  Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism. , 2005, Cardiovascular research.

[11]  J. Holloszy.  Exercise-induced increase in muscle insulin sensitivity. , 2005, Journal of applied physiology.

[12]  L. McCullough,et al.  Pharmacological Inhibition of AMP-activated Protein Kinase Provides Neuroprotection in Stroke* , 2005, Journal of Biological Chemistry.

[13]  C. Nielson,et al.  Blood glucose and heart failure in nondiabetic patients. , 2005, Diabetes care.

[14]  H. Ohgushi,et al.  Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. , 2004, American journal of physiology. Heart and circulatory physiology.

[15]  S. Kihara,et al.  Adiponectin-mediated modulation of hypertrophic signals in the heart , 2004, Nature Medicine.

[16]  D. Hardie.  The AMP-activated protein kinase pathway – new players upstream and downstream , 2004, Journal of Cell Science.

[17]  M. Birnbaum,et al.  AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. , 2004, The Journal of clinical investigation.

[18]  C. Gullion,et al.  The incidence of congestive heart failure in type 2 diabetes: an update. , 2004, Diabetes care.

[19]  J. Chrast,et al.  Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. , 2004, The Journal of clinical investigation.

[20]  D. V. van Veldhuisen,et al.  Alterations in the Prognosis of Chronic Heart Failure: An Overview of the Major Mortality Trials , 1997, Cardiovascular Drugs and Therapy.

[21]  D. Hardie.  Printed in U.S.A. Copyright © 2003 by The Endocrine Society doi: 10.1210/en.2003-0982 Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status , 2022 .

[22]  J. Connell,et al.  Direct Activation of AMP-activated Protein Kinase Stimulates Nitric-oxide Synthesis in Human Aortic Endothelial Cells* , 2003, Journal of Biological Chemistry.

[23]  N. Kimura,et al.  A possible linkage between AMP‐activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway , 2003, Genes to cells : devoted to molecular & cellular mechanisms.

[24]  Thomas D. Schmittgen,et al.  Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. , 2001, Methods.

[25]  Margaret S. Wu,et al.  Role of AMP-activated protein kinase in mechanism of metformin action. , 2001, The Journal of clinical investigation.

[26]  D. Carling,et al.  Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia , 2000, Current Biology.

[27]  M. Owen,et al.  Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. , 2000, The Biochemical journal.

[28]  M. Hoenig,et al.  Metformin improves vascular function in insulin-resistant rats. , 2000, Hypertension.

[29]  J. Ross,et al.  Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition. , 1999, Circulation.

[30]  G. Shulman,et al.  Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. , 1999, The American journal of physiology.

[31]  D. Hardie,et al.  AMP-activated protein kinase, a metabolic master switch: possible roles in Type 2 diabetes. , 1999, American journal of physiology. Endocrinology and metabolism.

[32]  P. Ortiz de Montellano,et al.  AMP‐activated protein kinase phosphorylation of endothelial NO synthase , 1999, FEBS letters.

[33]  R. Holman,et al.  Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) , 1998, The Lancet.

[34]  S. Anker,et al.  Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure. , 1997, Journal of the American College of Cardiology.

[35]  R. Marfella,et al.  Metformin Improves Hemodynamic and Rheological Responses to L-Arginine in NIDDM Patients , 1996, Diabetes Care.

[36]  R. V. Sharma,et al.  Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat. , 1996, American journal of hypertension.

[37]  A. M. Lefer,et al.  Attenuation of myocardial ischemia-reperfusion injury with nitric oxide replacement therapy. , 1995, The Annals of thoracic surgery.

[38]  G. Lopaschuk,et al.  High Rates of Fatty Acid Oxidation during Reperfusion of Ischemic Hearts Are Associated with a Decrease in Malonyl-CoA Levels Due to an Increase in 5′-AMP-activated Protein Kinase Inhibition of Acetyl-CoA Carboxylase (*) , 1995, The Journal of Biological Chemistry.

[39]  G. Paolisso,et al.  Insulin resistance and hyperinsulinemia in patients with chronic congestive heart failure. , 1991, Metabolism: clinical and experimental.

[40]  N. Reichek,et al.  Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society of Echocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. , 1989, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[41]  G. Reaven.  Role of Insulin Resistance in Human Disease , 1988, Diabetes.

[42]  H W Woo,et al.  Advantages and applications of the centerline method for characterizing regional ventricular function. , 1986, Circulation.

[43]  W. Kannel,et al.  Role of diabetes in congestive heart failure: the Framingham study. , 1974, The American journal of cardiology.

[44]  P. Trinder.  Determination of Glucose in Blood Using Glucose Oxidase with an Alternative Oxygen Acceptor , 1969 .