In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart

Physiological Reports

Adil Bashir¹  Andrew R. Coggan¹ 

[1] Cardiovascular Imaging Laboratory, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri

关键词: 31P;    creatine kinase flux;    diabetic cardiomyopathy;    heart;    type II diabetes;   

DOI  :  10.14814/phy2.12248

来源: Wiley

【 摘 要 】

Abstract

The effects of type II diabetes on cardiac creatine kinase (CK) enzyme activity and/or flux are unknown. We therefore measured steady-state phosphocreatine (PCr) and adenosine triphosphate (ATP) content and forward CK reaction kinetic parameters in Zucker Diabetic Fatty (ZDF) rat hearts, a type II diabetes research model. At baseline the PCr to ATP ratio (PCr/ATP) was significantly lower in diabetic heart when compared with matched controls (1.71 ± 0.21 vs. 2.26 ± 0.24, P < 0.01). Furthermore, the forward CK reaction rate constant (k_f) was higher in diabetic animals (0.52 ± 0.09 s⁻¹ vs. 0.35 ± 0.06 s⁻¹, P < 0.01) and CK flux calculated as a product of PCr concentration ([PCr]) and k_f was similar between two groups (4.32 ± 1.05 μmol/g/s vs. 4.94 ± 1.23 μmol/g/s, P = 0.20). Dobutamine administration resulted in similar increases in heart rate (~38%) and k_f (~0.12 s⁻¹) in both groups. No significant change in PCr and ATP content was observed with dobutamine. In summary, our data showed reduced PCr/ATP in diabetic myocardium as an indicator of cardiac energy deficit. The forward CK reaction rate constant is elevated at baseline which might reflect a compensatory mechanics to support energy flux through the CK shuttle and maintain constant ATP supply. When hearts were stimulated similar increase in k_f was observed in both groups thus it seems that CK shuttle does not limit ATP supply for the range of workload studied.

【 授权许可】

CC BY   
© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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