Howarth F C, Shafiullah M, Qureshi M A
Department of Physiology, Faculty of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
Exp Physiol. 2007 Nov;92(6):1029-36. doi: 10.1113/expphysiol.2007.038703. Epub 2007 Aug 3.
Type 2 diabetes mellitus accounts for more than 90% of all cases of diabetes mellitus, and cardiovascular complications are the major cause of mortality and death in diabetic patients. The chronic effects of type 2 diabetes mellitus on heart function have been investigated in the Goto-Kakizaki (GK) rat. Experiments were performed in GK rats and age-matched Wistar control rats at 18 months of age. The progressive effects of diabetes on glucose metabolism were monitored periodically by application of the glucose tolerance test. Ventricular action potentials were measured in isolated, perfused heart. Shortening and intracellular Ca(2+) were measured in electrically stimulated ventricular myocytes. The GK rats displayed mild fasting hyperglycaemia and progressively worsening glucose tolerance. At 18 months of age and 180 min after intraperitoneal injection of glucose (2 g (kg body weight)(-1)), blood glucose was 436 +/- 47 mg dl(-1) in GK rats compared with 153 +/- 18 mg dl(-1) in control animals. Heart weight to body weight ratio was significantly increased in GK rats (4.10 +/- 0.09 mg g(-1), n = 5) compared with control animals (3.36 +/- 0.22 mg g(-1), n = 4). Spontaneous heart rate was slightly reduced in GK rats compared with control rats. Although the amplitude of shortening was not altered, the amplitude of the Ca(2+) transient was significantly increased in myocytes from GK rats (0.78 +/- 0.11 ratio units) compared with control rats (0.50 +/- 0.06 ratio units). Despite progressively worsening glucose metabolism, at 18 months of age the contractile function of the heart appears to be well preserved.
2型糖尿病占所有糖尿病病例的90%以上，心血管并发症是糖尿病患者死亡和致死的主要原因。在Goto-Kakizaki（GK）大鼠中研究了2型糖尿病对心脏功能的慢性影响。实验在18月龄的GK大鼠和年龄匹配的Wistar对照大鼠中进行。通过应用葡萄糖耐量试验定期监测糖尿病对葡萄糖代谢的渐进性影响。在离体灌注心脏中测量心室动作电位。在电刺激的心室肌细胞中测量缩短和细胞内Ca(2+)。GK大鼠表现出轻度空腹高血糖，葡萄糖耐量逐渐恶化。在18月龄且腹腔注射葡萄糖（2 g (kg体重)(-1)）后180分钟，GK大鼠的血糖为436 +/- 47 mg dl(-1)，而对照动物为153 +/- 18 mg dl(-1)。与对照动物（3.36 +/- 0.22 mg g(-1)，n = 4）相比，GK大鼠的心脏重量与体重比显著增加（4.10 +/- 0.09 mg g(-1)，n = 5）。与对照大鼠相比，GK大鼠的自发心率略有降低。虽然缩短幅度没有改变，但与对照大鼠（0.50 +/- 0.06比值单位）相比，GK大鼠心肌细胞中Ca(2+)瞬变的幅度显著增加（0.78 +/- 0.11比值单位）。尽管葡萄糖代谢逐渐恶化，但在18月龄时心脏的收缩功能似乎仍保存良好。
