Metabolic disturbances in diabetic cardiomyopathy
Metabolic disturbances in diabetic cardiomyopathy
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DOI：
10.1023/a:1006882805197
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发表时间：
1998-03-01
影响因子：
4.3
通讯作者：
McNeill, JH
中科院分区：
文献类型：
--
作者：
Rodrigues, B;Cam, MC;McNeill, JH
已经确定糖尿病会导致心肌病，并且越来越多的证据表明心肌细胞底物供应和利用的改变可能是这种特定心肌疾病发病机制中的主要损伤。例如，在糖尿病中，葡萄糖的利用微不足道，能量产生几乎完全转向游离脂肪酸（FFA）的β-氧化。 FFA 有两个来源提供给心肌细胞：内源性心脏甘油三酯 (TG) 储存的脂解，或来自血液中的外源性来源（作为与白蛋白结合的游离酸或作为脂蛋白中的 TG）。外源性或内源性 FFA 对糖尿病心脏中 β-氧化的大致贡献尚不清楚。在胰岛素缺乏的状态下，脂肪组织的脂解作用增强，导致循环 FFA 升高。此外，增加的心肌TG储存的水解也可能导致高组织FFA。无论 FFA 的来源如何，它们的利用增加可能对心肌功能产生有害影响，包括 FFA 代谢过程中异常高的需氧量、FFA 潜在毒性中间体的细胞内积累、FFA 诱导的葡萄糖氧化抑制以及严重的形态变化。在糖尿病早期阶段针对心脏代谢异常的治疗可能会延迟或阻止更持久的后遗症的进展，而这些后遗症可能是由于心脏代谢紊乱而引起的。
It has been established that diabetes results in a cardiomyopathy, and increasing evidence suggests that an altered substrate supply and utilization by cardiac myocytes could be the primary injury in the pathogenesis of this specific heart muscle disease. For example, in diabetes, glucose utilization is insignificant, and energy production is shifted almost exclusively towards beta-oxidation of free fatty acids (FFA). FFA's are supplied to cardiac cells from two sources: lipolysis of endogenous cardiac triglyceride (TG) stores, or from exogenous sources in the blood (as free acid bound to albumin or as TG in lipoproteins). The approximate contribution of FFA from exogenous or endogenous sources towards beta-oxidation in the diabetic heart is unknown. In an insulin-deficient state, adipose tissue lipolysis is enhanced, resulting in an elevated circulating FFA. In addition, hydrolysis of the augmented myocardial TG stores could also lead to high tissue FFA. Whatever the source of FFA, their increased utilization may have deleterious effects on myocardial function and includes the abnormally high oxygen requirement during FFA metabolism, the intracellular accumulation of potentially toxic intermediates of FFA, a FFA-induced inhibition of glucose oxidation, and severe morphological changes. Therapies that target these metabolic aberrations in the heart during the early stages of diabetes could potentially delay or impede the progression of more permanent sequelae that could ensue from otherwise uncontrolled derangements in cardiac metabolism.