Mitochondria respiration and susceptibility to ischemia-reperfusion injury in diabetic hearts
Mitochondria respiration and susceptibility to ischemia-reperfusion injury in diabetic hearts
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DOI：
10.1016/j.abb.2003.09.024
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发表时间：
2003-12-15
影响因子：
3.9
通讯作者：
Romani, A
中科院分区：
文献类型：
--
作者：
Lashin, O;Romani, A
心血管并发症是糖尿病患者死亡的主要原因。临床和实验观察表明，功能失调性心肌病是糖尿病的主要并发症之一。心肌病是由于心肌组织对缺血性损伤的敏感性增加还是由于心肌线粒体的特定功能缺陷引起的，这是一个有争议的问题。对糖尿病大鼠心脏线粒体中可能的功能缺陷的研究表明，仅在体重显著下降的动物中，状态3呼吸下降。来自呈现与糖尿病动物相似的高血糖水平但不是后一组典型的显著体重减轻的大鼠的线粒体显示状态3呼吸没有下降，该值与对照线粒体的值不可区分。然而，来自高血糖大鼠的线粒体显示状态4氧消耗增加15-20%，但仅当谷氨酸盐用作能量底物时，相比之下，在类似的实验条件下，来自糖尿病大鼠的线粒体中状态4呼吸增加40-50%。这种现象与糖尿病病程无关，因为它在糖尿病发作后2周和8周观察到。总之，这些数据反对高血糖本身是在I型糖尿病大鼠的心脏线粒体中观察到的状态3耗氧量下降的直接原因，并表明一般标记为糖尿病的大鼠的心脏线粒体功能存在差异。这些差异有助于解释该领域不同小组报告的实验结果的差异，并提供了在评估糖尿病心脏对缺血再灌注损伤的不同敏感性时需要考虑的额外参数。(C)2003年爱思唯尔公司All rights reserved.
Cardiovascular complications are the primary cause of death for diabetic patients. Clinical and experimental observation has showed the development of dysfunctional cardiomyopathy as one of the main complications of diabetes. Whether the cardiomyopathy results from an increased susceptibility of cardiac tissue to ischemic insult or from a specific functional defect of cardiac mitochondria is a controversial issue. The investigation of possible functional defect in cardiac mitochondria from diabetic rats indicates a decline in state 3 respiration only in animals presenting a marked decrease in body weight. Mitochondria from rats presenting a level of hyperglycemia similar to diabetic animals but not the marked weight loss typical of the latter group show no decline in state 3 respiration, the values being indistinguishable from those of control mitochondria. Mitochondria from hyperglycemic rats, however, show a 15-20% increase in state 4 oxygen consumption but only when glutamate is used as energetic substrate, as compared to a 40-50% increase in state 4 respiration in mitochondria from diabetic rats under similar experimental conditions. This phenomenon is unrelated to diabetes duration, as it is observed at 2 as well as 8 weeks after diabetes onset. Taken together, these data argue against hyperglycemia per se being a direct cause of the decline in state 3 oxygen consumption observed in cardiac mitochondria of type-I diabetic rats and indicate that differences exist in cardiac mitochondrial function in rats generically labeled as diabetic. These differences can contribute to explain discrepancies in experimental results reported by various groups in the field and provide an additional parameter to be taken into consideration in evaluating the varying sensitivity of diabetic hearts to ischemia-reperfusion injury. (C) 2003 Elsevier Inc. All rights reserved.