The insulin sensitizer pioglitazone improves the deterioration of ischemic preconditioning in type 2 diabetes mellitus rats.

We investigated the effects of ischemic preconditioning (IP) on reperfusion arrhythmias in type 2 diabetic rats as well as the effects of the insulin sensitizer pioglitazone. Thirty-week-old OLETF rats with or without pioglitazone (10 mg/kgBW, orally) were used as a model for type 2 diabetes. LETO rats served as controls. The incidences and durations of reperfusion ventricular tachyarrhythmias (RVT) were evaluated using a working heart method. After 5 minutes of initial perfusion, the rats were divided into the following groups: 1) control rats without IP (CIP(-)), 2) control rats with IP (CIP(+)), 3) diabetic rats without IP (DIP(-)), 4) diabetic rats with IP (DIP(+)), 5) pioglitazone-treated diabetic rats without IP (TDIP(-)), and 6) pioglitazone-treated diabetic rats with IP (TDIP(+)). Three 2-minute cycles of global diastolic ischemia and 5 minutes of reperfusion before long ischemia were performed as IP. The incidence and duration of RVT in CIP(+) were significantly lower than in CIP(-). There was no significant difference in the duration of RVT between DIP(+) and DIP(-). However, the duration of RVT in TDIP(+) was significantly shorter than TDIP(-). These results suggested that the effects of IP on reperfusion arrhythmias are deteriorated in type 2 diabetic rats. The insulin sensitizer pioglitazone can improve the deterioration of IP against reperfusion arrhythmias in type 2 diabetic rats.

[1]  J. Snipes,et al.  Myocardial preconditioning against ischemia-reperfusion injury is abolished in Zucker obese rats with insulin resistance. , 2007, American journal of physiology. Regulatory, integrative and comparative physiology.

[2]  M. Hanefeld,et al.  Anti-inflammatory effects of pioglitazone and/or simvastatin in high cardiovascular risk patients with elevated high sensitivity C-reactive protein: the PIOSTAT Study. , 2007, Journal of the American College of Cardiology.

[3]  H. Yoshimatsu,et al.  Pioglitazone but Not Glibenclamide Improves Cardiac Expression of Heat Shock Protein 72 and Tolerance Against Ischemia/Reperfusion Injury in the Heredity Insulin-Resistant Rat , 2006, Diabetes.

[4]  T. Noda,et al.  Pioglitazone Ameliorates Insulin Resistance and Diabetes by Both Adiponectin-dependent and -independent Pathways* , 2006, Journal of Biological Chemistry.

[5]  N. Standen,et al.  Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium. , 2006, Cardiovascular research.

[6]  Erland Erdmann,et al.  Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial , 2005, The Lancet.

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

[8]  W. Koenig,et al.  Rapid Effects of Rosiglitazone Treatment on Endothelial Function and Inflammatory Biomarkers , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[9]  M. Mocanu,et al.  Preconditioning the diabetic heart: the importance of Akt phosphorylation. , 2005, Diabetes.

[10]  W. Bao,et al.  Rosiglitazone treatment in Zucker diabetic Fatty rats is associated with ameliorated cardiac insulin resistance and protection from ischemia/reperfusion-induced myocardial injury. , 2005, Diabetes.

[11]  H. Bøtker,et al.  Ischaemic preconditioning does not protect the heart in obese and lean animal models of Type 2 diabetes , 2004, Diabetologia.

[12]  P. Scherer,et al.  Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. , 2004, Diabetes.

[13]  S. Cuzzocrea,et al.  Absence of inducible nitric oxide synthase reduces myocardial damage during ischemia reperfusion in streptozotocin-induced hyperglycemic mice. , 2004, Diabetes.

[14]  Johan Auwerx,et al.  Activation of peroxisome proliferator-activated receptor δ induces fatty acid β-oxidation in skeletal muscle and attenuates metabolic syndrome , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[15]  M. Mozaffari,et al.  Effect of Hypertension and Hypertension-Glucose Intolerance on Myocardial Ischemic Injury , 2003, Hypertension.

[16]  M. Matsuda,et al.  Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. , 2003, Diabetes.

[17]  T. Bohlen,et al.  Effect of acute hyperglycaemia and diabetes mellitus with and without short-term insulin treatment on myocardial ischaemic late preconditioning in the rabbit heart in vivo , 2003, Pflügers Archiv.

[18]  Jasmine Chen,et al.  Constitutive Activation of Peroxisome Proliferator-activated Receptor-γ Suppresses Pro-inflammatory Adhesion Molecules in Human Vascular Endothelial Cells* , 2002, The Journal of Biological Chemistry.

[19]  M. Jiménez-Navarro,et al.  Does angina pectoris the week before protect against first acute myocardial infarction in patients with diabetes mellitus? , 2002, The American journal of cardiology.

[20]  K. Clarke,et al.  Thiazolidinedione treatment normalizes insulin resistance and ischemic injury in the zucker Fatty rat heart. , 2002, Diabetes.

[21]  T. Saruta,et al.  Effects of pioglitazone on metabolic parameters, body fat distribution, and serum adiponectin levels in Japanese male patients with type 2 diabetes. , 2002, Metabolism: clinical and experimental.

[22]  K. Nishioka,et al.  Diabetes mellitus prevents ischemic preconditioning in patients with a first acute anterior wall myocardial infarction. , 2001, Journal of the American College of Cardiology.

[23]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[24]  任艳,et al.  胰岛素增敏剂一Thiazolidinediones研究现状 , 2000 .

[25]  A. Ziegelhöffer,et al.  Acute diabetes modulates response to ischemia in isolated rat heart , 2000, Molecular and Cellular Biochemistry.

[26]  Sander Kersten,et al.  Roles of PPARs in health and disease , 2000, Nature.

[27]  P. Pagel,et al.  Diabetes abolishes ischemic preconditioning: role of glucose, insulin, and osmolality. , 2000, American journal of physiology. Heart and circulatory physiology.

[28]  K. Shimamoto,et al.  Reperfusion arrhythmias in the murine heart: their characteristics and alteration after ischemic preconditioning , 1999, Basic Research in Cardiology.

[29]  R. Ramasamy,et al.  Inhibition of Na+-H+ exchanger protects diabetic and non-diabetic hearts from ischemic injury: insight into altered susceptibility of diabetic hearts to ischemic injury. , 1999, Journal of molecular and cellular cardiology.

[30]  T. Nishimura,et al.  Difference in the mechanisms for compensating ischemic acidosis in diabetic rat hearts. , 1998, Journal of Molecular and Cellular Cardiology.

[31]  T. Tanaka,et al.  Energy metabolism after ischemic preconditioning in streptozotocin-induced diabetic rat hearts. , 1998, Journal of the American College of Cardiology.

[32]  J. Russell,et al.  Postischemic cardiac performance in the insulin-resistant JCR:LA-cp rat. , 1997, The American journal of physiology.

[33]  R. Califf,et al.  Influence of Diabetes Mellitus on Clinical Outcome in the Thrombolytic Era of Acute Myocardial Infarction , 1997 .

[34]  T. Mcdonald,et al.  Protection by hypoxic preconditioning against hypoxia-reoxygenation injury in guinea-pig papillary muscles. , 1997, Cardiovascular research.

[35]  D. Feuvray.  The regulation of intracellular pH in the diabetic myocardium. , 1997, Cardiovascular research.

[36]  Á. Tósaki,et al.  The evolution of diabetic response to ischemia/reperfusion and preconditioning in isolated working rat hearts. , 1996, Cardiovascular research.

[37]  M. Moghadasian,et al.  Gender-related regional antioxidant profiles in the gastrointestinal tract of the rat , 1996, Molecular and Cellular Biochemistry.

[38]  D. Hearse,et al.  Three questions about preconditioning , 1996, Basic Research in Cardiology.

[39]  M. Bernard,et al.  Mechanisms of Intracellular pH Regulation During Postischemic Reperfusion of Diabetic Rat Hearts , 1995, Diabetes.

[40]  G. Lopaschuk,et al.  Glycolysis and glucose oxidation during reperfusion of ischemic hearts from diabetic rats. , 1994, Biochimica et biophysica acta.

[41]  J. Downey,et al.  Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction. , 1993, Circulation.

[42]  D. Ramsdale,et al.  Free-radical generation during angioplasty reperfusion for acute myocardial infarction , 1993, The Lancet.

[43]  G. Lopaschuk,et al.  Effects of high levels of fatty acids on functional recovery of ischemic hearts from diabetic rats. , 1992, The American journal of physiology.

[44]  K. Kawano,et al.  Spontaneous Long-Term Hyperglycemic Rat With Diabetic Complications: Otsuka Long-Evans Tokushima Fatty (OLETF) Strain , 1992, Diabetes.

[45]  S. Komori,et al.  Protective effect of preconditioning on reperfusion induced ventricular arrhythmias of isolated rat hearts. , 1991, Cardiovascular research.

[46]  F. Marumo,et al.  Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes. , 1990, Circulation research.

[47]  L. Opie,et al.  Effects of proton buffering and of amiloride derivatives on reperfusion arrhythmias in isolated rat hearts. Possible evidence for an arrhythmogenic role of Na(+)-H+ exchange. , 1990, Circulation research.

[48]  M. Tani,et al.  Hearts From Diabetic Rats Are More Resistant to In Vitro Ischemia: Possible Role of Altered Ca2+ Metabolism , 1988, Circulation research.

[49]  R. Jennings,et al.  Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. , 1986, Circulation.

[50]  M. Bernier,et al.  Reperfusion‐induced Arrhythmias and Oxygen‐derived Free Radicals: Studies with “Anti‐Free Radical” Interventions and a Free Radical‐generating System in the Isolated Perfused Rat Heart , 1986, Circulation research.

[51]  D. Coltart,et al.  Ischemia and reperfusion-induced arrhythmias in the rat. Effects of xanthine oxidase inhibition with allopurinol. , 1984, Circulation research.

[52]  J. J. Spadaro,et al.  Increased congestive heart failure after myocardial infarction of modest extent in patients with diabetes mellitus. , 1984, American heart journal.

[53]  A. Noma,et al.  ATP-regulated K+ channels in cardiac muscle , 1983, Nature.

[54]  G. Wahler,et al.  ATP-sensitive potassium channels are altered in ventricular myocytes from diabetic rats , 1979, Molecular and Cellular Biochemistry.

[55]  R. S. Eliot,et al.  Reduced high-energy phosphate levels in rat hearts. I. Effects of alloxan diabetes. , 1976, The American journal of physiology.

[56]  M. Rovetto,et al.  Effects of ischemia on function and metabolism of the isolated working rat heart. , 1973, The American journal of physiology.

[57]  E. Lascano,et al.  Absence of ischemic preconditioning protection in diabetic sheep hearts: Role of sarcolemmal KATP channel dysfunction , 2004, Molecular and Cellular Biochemistry.

[58]  J. Auwerx,et al.  Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome. , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Yongge Liu,et al.  Roles of mitochondrial ATP-sensitive K channels and PKC in anti-infarct tolerance afforded by adenosine A1 receptor activation. , 2000, Journal of the American College of Cardiology.

[60]  A. Ziegelhöffer,et al.  Susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic rat heart. , 2000, Physiological research.

[61]  Teven,et al.  MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION , 2000 .

[62]  D. Lamontagne,et al.  Protection afforded by preconditioning to the diabetic heart against ischaemic injury. , 1998, Cardiovascular research.

[63]  B. Seed,et al.  PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. , 1998, Nature.

[64]  S. Vatner,et al.  Stunning, hibernation, and preconditioning : clinical pathophysiology of myocardial ischemia , 1997 .

[65]  R. Califf,et al.  Influence of diabetes mellitus on clinical outcome in the thrombolytic era of acute myocardial infarction. GUSTO-I Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. , 1997, Journal of the American College of Cardiology.

[66]  D. Spray,et al.  Physiology and pharmacology of gap junctions. , 1985, Annual review of physiology.

[67]  V. Polezhaev.  Effect of a , 1974 .