Cardiac dysfunction in the Goto-Kakizaki rat - A model of type II diabetes mellitus
Cardiac dysfunction in the Goto-Kakizaki rat - A model of type II diabetes mellitus
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DOI：
10.1007/s00395-004-0440-4
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发表时间：
2004-03-01
影响因子：
9.5
通讯作者：
Shah, AM
中科院分区：
文献类型：
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作者：
El-Omar, MM;Yang, ZK;Shah, AM
糖尿病心脏中心脏功能的实验研究主要集中在I型糖尿病模型上。我们研究了Goto-Kakizaki（GK）大鼠的心脏功能，GK大鼠是一种自发性非肥胖II型糖尿病的近交系模型。方法：研究了GK和对照Wistar大鼠心脏的离体灌流心脏和离体心室肌细胞。在一定范围的刺激频率（0.5-2.5 Hz; 32 ℃，n = 16-24个细胞）下测量肌细胞收缩缩短百分比（%TS）和相应的细胞内钙瞬变（indo-1荧光比，R）。在离体Langendorff灌注心脏中，我们测量了基线和短暂（10分钟）缺氧期间的左室收缩压（LVPmax）、左室舒张末期压（LVEDP）、左室压力上升（LV dP/dt（max））和下降（LV dP/dt（min））的最大速率以及等容左室舒张（指数时间常数，T）。结果：在所有刺激频率下，GK和对照肌细胞之间的%TS和相应的indo-1 R相似（例如，在2.5 Hz下：GK和对照分别为% TS = 8.6 +/- 0.77和8.2 +/- 0.19; R = 0.19 +/- 0.009和0.18 +/- 0.018，P = NS）。同样，基线LVPmax无显著差异，（分别为129 +/- 6.2和135 +/- 9.6 mmHg; GK和对照，P = NS），LV dP/dt（最大值）（分别为3169.5 +/- 165.80和3390.6 +/- 232.60 mmHg/s; GK和对照，P = NS），LV dP/dt（min）或T（分别为24 +/- 0.7和25 +/- 0.6 ms，GK和对照，P = NS）。缺氧10 min时，GK组左室dP/dt（max）较对照组显著降低，LVEDP和T较对照组显著升高（左室dP/dt（最大值）：668.90 +/- 32.8 vs 1027.10 +/- 84.0 mmHg/s;左室舒张末压：21.4 +/- 4.3 vs 11.6 +/- 0.6 mmHg; T：102 +/- 13.8 vs 56 +/- 3.0 ms; GK vs对照; P均< 0.05）。GK心脏的这些异常在急性加入胰岛素（0.01 i. u./ ml）加入到灌注缓冲液中。结论：II型糖尿病的GK模型显示出轻度心肌病，其明显表现为缺氧期间过度的舒张功能障碍。该机制可能涉及底物决定性。
Experimental study of cardiac function in the diabetic heart has focussed mostly on models of Type I diabetes. We studied cardiac function in the Goto-Kakizaki (GK) rat, an inbred model of spontaneous non-obese, Type II diabetes. Methods:. Both isolated perfused hearts and isolated ventricular myocytes from GK and matched control Wistar rat hearts were studied. Percent myocyte twitch shortening (%TS) and corresponding intracellular calcium transients (indo-1 uorescence ratio, R) were measured over a range of stimulation frequencies (0.5-2.5 Hz; 32 degreesC, n = 16-24 cells). In isolated Langendorff-perfused hearts, we measured systolic LV pressure (LVPmax), left ventricular end diastolic pressure (LVEDP), maximal rate of LV pressure rise (LV dP/dt(max)) and fall (LV dP/dt(min)) and isovolumic LV relaxation (exponential time constant, T) both at baseline and during brief (10 minutes) hypoxia. Results:. The %TS and corresponding indo-1 R were similar between GK and control myocytes at all stimulation frequencies (e.g. at 2.5 Hz: % TS = 8.6 +/- 0.77 and 8.2 +/- 0.19; R = 0.19 +/- 0.009 and 0.18 +/- 0.018, GK and control respectively, P = NS). Similarly, there were no signicant differences in baseline LVPmax (129 +/- 6.2 and 135 +/- 9.6 mmHg; GK and control respectively, P = NS), LV dP/dt(max) (3169.5 +/- 165.80 and 3390.6 +/- 232.60 mmHg/s; GK and control respectively, P = NS), LV dP/dt(min) or T (24 +/- 0.7 and 25 +/- 0.6 ms, GK and control respectively, P = NS). During 10 min hypoxia, LV dP/dt(max) decreased signicantly more, and LVEDP and T increased signi- cantly more, in GK compared to control hearts (LV dP/dt(max): 668.90 +/- 32.8 versus 1027.10 +/- 84.0 mmHg/s; LVEDP: 21.4 +/- 4.3 versus 11.6 +/- 0.6 mmHg; T: 102 +/- 13.8 versus 56 +/- 3.0 ms; GK versus control respectively; all P < 0.05). These abnormalities in GK hearts were reversed with acute addition of insulin (0.01 i. u./ml) to the perfusion buffer. Conclusion:. The GK model of Type II diabetes displays a mild cardiomyopathy evident as exaggerated diastolic dysfunction during hypoxia. The mechanism is likely to involve substrate deciency.