Makino N, Dhalla K S, Elimban V, Dhalla N S
Am J Physiol. 1987 Aug;253(2 Pt 1):E202-7. doi: 10.1152/ajpendo.1987.253.2.E202.
Heart sarcolemmal membranes were isolated by the sucrose density gradient method from rats with chronic diabetes induced by a streptozotocin (65 mg/kg iv) injection. Na+-dependent Ca2+-uptake activities were significantly depressed in diabetic sarcolemmal membranes; such alterations were evident at different incubation times and at different concentrations of Ca2+. Administration of insulin to diabetic rats normalized the Na+-dependent Ca2+-uptake activities. ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent ATPase, which represents Ca2+-pump mechanisms, were significantly depressed in sarcolemmal preparations for diabetic rats and these changes were also reversible upon insulin treatment. An increase in lysophosphatidylcholine and a decrease in phosphatidylethanolamine as well as diphosphatidylglycerol contents were observed in heart membranes isolated from diabetic rats but other phospholipids were unchanged. Cholesterol-to-phospholipid ratio was significantly increased in preparations from diabetic rats. These results indicate a depression in the ability of the cell to remove Ca2+ through Na+-Ca2+ exchange and Ca2+-pump mechanisms in sarcolemma, and these defects may contribute to the occurrence of intracellular Ca2+ overload and diabetic cardiomyopathy.
通过蔗糖密度梯度法从经链脲佐菌素（65mg/kg静脉注射）诱导的慢性糖尿病大鼠中分离出心脏肌膜。糖尿病肌膜中钠依赖性钙摄取活性显著降低；在不同的孵育时间和不同的钙浓度下，这种改变都很明显。给糖尿病大鼠注射胰岛素可使钠依赖性钙摄取活性恢复正常。在糖尿病大鼠的肌膜制剂中，依赖ATP的钙积累和代表钙泵机制的钙刺激的镁依赖性ATP酶显著降低，并且这些变化在胰岛素治疗后也是可逆的。在从糖尿病大鼠分离的心脏膜中观察到溶血磷脂酰胆碱增加、磷脂酰乙醇胺以及二磷脂酰甘油含量降低，但其他磷脂未发生变化。糖尿病大鼠制剂中的胆固醇与磷脂比率显著增加。这些结果表明细胞通过肌膜中的钠-钙交换和钙泵机制去除钙的能力降低，并且这些缺陷可能导致细胞内钙超载和糖尿病性心肌病的发生。
