Creatine kinase kinetics in diabetic cardiomyopathy.
One feature of the diabetic cardiomyopathy is the appearance of contractile dysfunction as the workload increases. We hypothesized that this resulted from an impaired creatine kinase/phosphocreatine system and therefore examined the creatine kinase kinetics at both low and high workloads. Creatine kinase flux (by 31P nuclear magnetic resonance saturation transfer method), cardiac performance, and oxygen consumption were measured in control and streptozotocin-induced diabetic rat hearts. Creatine kinase flux was inhibited by iodoacetamide in control hearts to confirm the role of the creatine kinase/phosphocreatine system in cardiac performance. In diabetic hearts, 1) the contractile dysfunction became apparent only at high workloads, 2) the ATP synthesis rate was not significantly different from control hearts, 3) the creatine kinase flux was reduced by 30.8% (257.5 +/- 7.7 mumol.g wet wt-1.min-1 in control vs. 178.3 +/- 9.4 in diabetes, P < 0.001), and 4) the creatine kinase flux did not increase as the workload increased. In control hearts, 5) iodoacetamide inhibited the creatine kinase flux to the same degree as that in diabetic hearts, and 6) the contractile dysfunction was not as severe as that observed in diabetic hearts. These results suggest that the impaired creatine kinase/phosphocreatine system is, at least in part, responsible for the contractile dysfunction in the diabetic cardiomyopathy.
Matsumoto
Y
Y
Third Department of Internal Medicine and Chemistry, Hamamatsu University School of Medicine, Japan.
Kaneko
M
M
Kobayashi
A
A
Fujise
Y
Y
Yamazaki
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D009202:Cardiomyopathies / Q000201:enzymology* / Q000503:physiopathology*; D003402:Creatine Kinase / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000503:physiopathology; D006321:Heart / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D066298:In Vitro Techniques; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009206:Myocardium / Q000201:enzymology; D010477:Perfusion; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012044:Regression Analysis; D016277:Ventricular Function, Left
D007461:Iodoacetates; D010710:Phosphates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase; D019807:Iodoacetic Acid