In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart.
In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart.
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DOI：
10.14814/phy2.12248
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发表时间：
2015-01-01
影响因子：
2.5
通讯作者：
Gropler RJ
中科院分区：
文献类型：
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作者：
Bashir A;Coggan AR;Gropler RJ
II型糖尿病对心肌肌酸激酶（CK）酶活性和/或流量的影响尚不清楚。因此，我们测量了Zucker糖尿病脂肪（ZDF）大鼠心脏（一种II型糖尿病研究模型）的稳态磷酸肌酸（PCr）和三磷酸腺苷（ATP）含量以及正向CK反应动力学参数。糖尿病组基线时PCr/ATP比值（1.71 ± 0.21）显著低于对照组（2.26 ± 0.24）（P < 0.01）。糖尿病动物的前向CK反应速率常数（kf）明显升高（0.52 ± 0.09 s-1 vs. 0.35 ± 0.06 s-1，P < 0.01），两组间以PCr浓度（[PCr]）和kf的乘积计算的CK通量相似（4.32 ± 1.05 μmol/g/s vs.4.94 ± 1.23 μmol/g/s，P = 0.20）。多巴酚丁胺给药导致两组心率（~38%）和kf（~0.12 s-1）增加相似。多巴酚丁胺对PCr和ATP含量无明显影响。总之，我们的数据显示糖尿病心肌中PCr/ATP降低是心脏能量不足的指标。前向CK反应速率常数在基线时升高，这可能反映了一种补偿机制，以支持通过CK穿梭的能量通量并维持恒定的ATP供应。当心脏被刺激时，在两组中观察到类似的kf增加，因此似乎CK穿梭并不限制所研究的工作负荷范围内的ATP供应。应用无创性31 PMRS检测2型糖尿病大鼠心肌PCr浓度（[PCr]）和肌酸激酶（CK）反应流。[PCr]与对照组相比，在糖尿病心肌中降低，表明线粒体ATP产生受损。前向CK反应速率常数升高，可能反映了一种代偿机制，以支持通过CK穿梭所需的支持心脏工作的流量增加。CK反应速度在糖尿病和对照心脏增加，以维持恒定的ATP含量在较高的工作。
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 (kf) 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 kf 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 kf (~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 kf was observed in both groups thus it seems that CK shuttle does not limit ATP supply for the range of workload studied. Noninvasive 31P MRS was used to measure PCr concentration ([PCr]) and creatine kinase (CK) reaction flux in type II diabetic rat hearts. [PCr] was reduced in diabetic myocardium as compared to controls, indicative of impairment in mitochondrial ATP production. The forward CK reaction rate constant was elevated, possibly reflecting a compensatory mechanism to support increased flux through the CK shuttle required to support cardiac work. CK reaction velocity increased in both diabetic and control hearts to maintain constant ATP content at higher work.