Cardiomyocyte dysfunction in insulin-resistant rats: a female advantage.
Cardiomyocyte dysfunction in insulin-resistant rats: a female advantage.
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胰岛素抵抗大鼠的心肌细胞功能障碍：女性优势。
DOI：
10.1007/s00125-006-0184-9
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发表时间：
2006
期刊：
影响因子：
8.2
通讯作者：
Davidoff,AJ
中科院分区：
文献类型：
--
作者：
Schwanke,ML;Dutta,K;Podolin,DA;Davidoff,AJ
Aims/hypothesis本调查的目的是确定是否有性别相关的差异，在糖尿病前期，insulin-resistant animals.Materials和methodsMale和female大鼠的心肌细胞功能障碍的发展维持在一个高蔗糖饮食5-11周，和机械性能的分离心室肌细胞进行了测量，通过高速视频边缘检测。几种体外干预措施被用来操纵细胞内钙离子，以确定是否改变钙离子的可用性有助于心肌细胞dysfunction.ResultsMyocyte shortening和relengthening显着缓慢蔗糖喂养（胰岛素抵抗）的男性比在淀粉喂养（正常）的雄性大鼠，而只有relengthening是缓慢的蔗糖喂养的女性相比，正常女性。蔗糖喂养的男性的收缩和舒张阶段下的区域也显着大于饮食匹配的女性，并且男性的心肌细胞力学减慢出现得更早（7周vs 10周）。所有干预措施（即10− 8 mol/l异丙肾上腺素、升高的细胞外Ca 2+和更高的刺激率）均改善了蔗糖喂养雌性大鼠的肌细胞的长时间舒张。细胞外Ca 2+的两倍（4 mmol/l）是恢复正常的时间进程的收缩和舒张在蔗糖喂养的男性比在女性，和机械反应，以更高的频率刺激仍然受损（慢）在一些肌细胞从蔗糖喂养的雄性rats.Conclusions/interpretationThese数据表明，在肌细胞从胰岛素抵抗大鼠改变钙处理发生，有助于异常兴奋-收缩偶联;雌性大鼠在向2型糖尿病发展的早期阶段似乎具有一定的心脏保护作用。女性表现出延迟发病和代谢状态和心肌细胞功能的轻度异常，但这些功能障碍的时间耦合更紧密。
Aims/hypothesisThe goal of this investigation was to determine whether there are sex-related differences in the development of cardiomyocyte dysfunction in prediabetic, insulin-resistant animals.Materials and methodsMale and female rats were maintained on a high-sucrose diet for 5–11 weeks, and mechanical properties of isolated ventricular myocytes were measured by high-speed video edge detection. Several in vitro interventions were used to manipulate intracellular Ca2+in order to determine whether altered Ca2+availability contributes to the cardiomyocyte dysfunction.ResultsMyocyte shortening and relengthening were significantly slower in sucrose-fed (insulin-resistant) males than in starch-fed (normal) male rats, whereas only relengthening was slower in sucrose-fed females when compared with normal females. Areas under the contraction and relaxation phases for sucrose-fed males were also significantly larger than in diet-matched females, and the slowed cardiomyocyte mechanics appeared earlier in males (7 vs 10 weeks). Prolonged relaxation was ameliorated in myocytes from sucrose-fed female rats by all interventions (i.e. 10−8mol/l isoprenaline, elevated extracellular Ca2+, and higher rates of stimulation). Twice as much extracellular Ca2+(4 mmol/l) was required to restore normal time courses of contraction and relaxation in sucrose-fed males than in females, and mechanical responses to higher frequency stimulation remained impaired (slower) in some myocytes from sucrose-fed male rats.Conclusions/interpretationThese data suggest that in myocytes from insulin-resistant rats altered Ca2+handling occurs, contributing to abnormal excitation–contraction coupling; female rats seem to have some cardioprotection during early stages in the progression towards type 2 diabetes. Females show delayed onset and milder abnormalities in metabolic status and cardiomyocyte function, but with a much tighter temporal coupling of these dysfunctions.