Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart.
Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart.
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DOI：
10.1016/j.jacc.2009.07.031
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发表时间：
2009-11-10
影响因子：
24
通讯作者：
Neufer, P. Darrell
中科院分区：
文献类型：
--
作者：
Anderson, Ethan J.;Kypson, Alan P.;Rodriguez, Evelio;Anderson, Curtis A.;Lehr, Eric J.;Neufer, P. Darrell
本研究的目的是确定糖尿病对2型糖尿病患者心肌中碳水化合物和脂质基质的氧化平衡和线粒体代谢的影响。心力衰竭是糖尿病患者死亡的一个主要原因，有人提出心脏代谢和氧化应激紊乱可能是这种合并症进展的基础，但很少有证据支持人类的这一机制。非糖尿病（n=13）和糖尿病（n=11）接受非紧急冠状动脉搭桥手术的患者右心耳样品制备的渗透肌纤维中线粒体O2消耗和H2O2排放的测量。与非糖尿病患者相比，2型糖尿病患者心房组织中的线粒体谷氨酸和脂肪酸支持呼吸能力急剧下降，心肌甘油三酯含量增加。此外，糖尿病患者在碳水化合物和脂质基质氧化过程中，线粒体H2O2排放增加，谷胱甘肽耗竭，心房组织持续氧化应激。这些发现是第一次使用细胞和分子方法直接研究2型糖尿病对人类心肌线粒体功能的影响，他们证明糖尿病人心脏中的线粒体在最大氧化脂肪酸和谷氨酸的能力方面存在特异性损伤，但线粒体H2O2排放增加。提供线粒体功能障碍和氧化应激在糖尿病患者心力衰竭发病机制中的作用。
This aim of this study was to determine the impact of diabetes on oxidant balance and mitochondrial metabolism of carbohydrate- and lipid-based substrates in myocardium of type 2 diabetic patients. Heart failure represents a major cause of death among diabetics, and it has been proposed that derangements in cardiac metabolism and oxidative stress may underlie the progression of this co-morbidity, but scarce evidence exists in support of this mechanism in humans. Mitochondrial O2 consumption and H2O2 emission were measured in permeabilized myofibers prepared from samples of right atrial appendage obtained from non-diabetic (n=13) and diabetic (n=11) patients undergoing non-emergent coronary artery bypass graft surgery. Mitochondria in atrial tissue of type 2 diabetic individuals display a sharply decreased capacity for glutamate and fatty acid-supported respiration, in addition to an increased content of myocardial triglycerides, as compared to non-diabetics. Furthermore, diabetics display an increased mitochondrial H2O2 emission during oxidation of carbohydrate- and lipid-based substrates, depleted glutathione, and evidence of persistent oxidative stress in their atrial tissue. These findings are the first to directly investigate the effects of type 2 diabetes on a panoply of mitochondrial functions in the human myocardium using cellular and molecular approaches, and they demonstrate that mitochondria in diabetic human heart have specific impairments in maximal capacity to oxidize fatty acids and glutamate, yet increased mitochondrial H2O2 emission, providing insight into the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of heart failure in diabetic patients.
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DOI：
10.1016/0005-2728(93)90166-d
发表时间：
1993-09-13
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
SAKS, VA;VASILEVA, E;PEROV, NA
通讯作者：
PEROV, NA
影响因子：
7.7
作者：
Young, ME;Guthrie, PH;Taegtmeyer, H
通讯作者：
Taegtmeyer, H
影响因子：
15.9
作者：
Anderson, Ethan J.;Lustig, Mary E.;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell
影响因子：
2.1
作者：
Severson, DL
通讯作者：
Severson, DL
影响因子：
4.8
作者：
Anderson, Ethan J.;Yamazaki, Hanae;Neufer, P. Darrell
通讯作者：
Neufer, P. Darrell