Sucrose-induced cardiomyocyte dysfunction is both preventable and reversible with clinically relevant treatments
Sucrose-induced cardiomyocyte dysfunction is both preventable and reversible with clinically relevant treatments
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DOI：
10.1152/ajpendo.00358.2003
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发表时间：
2004-05-01
影响因子：
5.1
通讯作者：
Ren, J
中科院分区：
文献类型：
--
作者：
Davidoff, AJ;Mason, MM;Ren, J
我们最近确定了2型糖尿病早期的心肌细胞功能障碍（即，饮食诱导的胰岛素抵抗）。本研究旨在确定各种临床相关干预措施是否足以预防和逆转蔗糖（SU）喂养的胰岛素抵抗大鼠的心肌细胞功能障碍。允许动物亚组运动（自由接近连接到笼子的轮子）或在饮用水中用苯扎贝特治疗，以确定这些干预措施是否会防止SU喂养对心肌细胞功能的不良影响。饮食和治疗6 - 8周后，通过手术准备动物以评估全身胰岛素敏感性（静脉内葡萄糖耐量试验），并评估分离的心室肌细胞力学（视频边缘记录）。SU喂养产生高胰岛素血症和高胰岛素血症，并伴有胰岛素抵抗，诱导特征性全身胰岛素抵抗。运动和苯扎贝特治疗预防了这些代谢异常。与淀粉（ST）喂养的对照组相比，SU喂养的大鼠（42-63%）的心室肌细胞缩短和再延长较慢，运动或苯扎贝特完全防止了SU喂养大鼠的心肌细胞功能障碍。在单独的动物队列中，在SU喂养5周后，将动物转回ST饮食或给予鲱鱼油额外7-9周，以确定心肌细胞功能障碍是否可逆。这两种干预措施先前已被证明具有有利的代谢作用，并且都改善了心肌细胞力学，但只有ST饮食逆转了SU喂养诱导的心肌细胞功能障碍的所有迹象。因此，发现与2型糖尿病早期阶段相关的心肌细胞力学的表型变化通过临床相关治疗是可预防和可逆的，这表明导致这种功能障碍的细胞过程是可改变的。
We recently identified cardiomyocyte dysfunction in the early stage of type 2 diabetes (i.e., diet-induced insulin resistance). The present investigation was designed to determine whether a variety of clinically relevant interventions are sufficient to prevent and reverse cardiomyocyte dysfunction in sucrose (SU)-fed insulin-resistant rats. Subsets of animals were allowed to exercise (free access to wheel attached to cage) or were treated with bezafibrate in drinking water to determine whether these interventions would prevent the adverse effects of SU feeding on cardiomyocyte function. After 6 - 8 wk on diet and treatment, animals were surgically prepared to assess whole body insulin sensitivity (intravenous glucose tolerance test), and isolated ventricular myocyte mechanics were evaluated (video edge recording). SU feeding produced hyperinsulinemia and hypertriglyceridemia, with euglycemia, and induced characteristic whole body insulin resistance. Both exercise and bezatibrate treatment prevented these metabolic abnormalities. Ventricular myocyte shortening and relengthening were slower in SU-fed rats (42-63%) compared with starch (ST)-fed controls, and exercise or bezafibrate completely prevented cardiomyocyte dysfunction in SU-fed rats. In separate cohorts of animals, after 5 wk of SU feeding, animals were either switched back to an ST diet or given menhaden oil for an additional 7-9 wk to determine whether the cardiomyocyte dysfunction was reversible. Both interventions have previously been shown to have favorable metabolic effects, and both improved myocyte mechanics, but only the ST diet reversed all indications of cardiomyocyte dysfunction induced by SU feeding. Thus phenotypic changes in cardiomyocyte mechanics associated with early stages of type 2 diabetes were found to be both preventable and reversible with clinically relevant treatments, suggesting that the cellular processes contributing to this dysfunction are modifiable.