Golfman L S, Takeda N, Dhalla N S
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Diabetes Res Clin Pract. 1996 Jul;31 Suppl:S73-7. doi: 10.1016/0168-8227(96)01233-8.
In order to determine if cardiac membrane Ca(2+)-transport activities are altered in chronic diabetes induced by alloxan, rats were given an intravenous injection of 65 mg/kg and the hearts were used 8 weeks later. Some 4 weeks, diabetic animals were injected with insulin (3 U/day) for 4 weeks. Both sarcolemmal (SL) and sarcoplasmic reticulum (SR) membranes were isolated from the ventricular tissue and their Ca(2+)-transporting activities were determined. SL Na(+)-dependent Ca2+ uptake, ATP-dependent Ca2+ uptake and Ca(2+)-stimulated ATPase activities were depressed in the diabetic heart. Likewise, SR ATP-dependent Ca2+ uptake activity in the diabetic heart was markedly decreased in comparison to the control preparations. These defects in diabetic SL and SR Ca(2+)-transport activities were prevented by treatment of diabetic animals with insulin. The results from the alloxan-rat model of diabetes support the view that membrane abnormalities with respect to Ca2+ handling may lead to the occurrence of intracellular Ca2+ overload and the development of diabetic cardiomyopathy.
为了确定四氧嘧啶诱导的慢性糖尿病大鼠心脏膜钙转运活性是否发生改变，给大鼠静脉注射65mg/kg四氧嘧啶，8周后取心脏。约4周时，给糖尿病动物注射胰岛素（3U/天），持续4周。从心室组织中分离出肌膜（SL）和肌浆网（SR）膜，并测定其钙转运活性。糖尿病心脏中，肌膜的钠依赖性钙摄取、ATP依赖性钙摄取和钙刺激的ATP酶活性均降低。同样，与对照制剂相比，糖尿病心脏中肌浆网的ATP依赖性钙摄取活性显著降低。用胰岛素治疗糖尿病动物可预防糖尿病肌膜和肌浆网钙转运活性的这些缺陷。四氧嘧啶诱导的糖尿病大鼠模型的结果支持这样一种观点，即钙处理方面的膜异常可能导致细胞内钙超载的发生和糖尿病心肌病的发展。
