Nuwayri-Salti Nuha, Karam Chehade N, Al Jaroudi Wael A, Usta Julnar A, Maharsy Wael M, Bitar Khalil M, Bikhazi Anwar B
Department of Human Morphology, American University of Beirut, Beirut, Lebanon.
Can J Physiol Pharmacol. 2007 Feb;85(2):215-24. doi: 10.1139/y07-012.
This project assesses the treatment role with insulin and (or) angiotensin II receptor subtype-1 (AT1-R) blocker (ARB) on insulin receptor and endothelin-1 receptor subtype (ETA-R and ETB-R) regulation in rat hearts suffering from insulin-dependent diabetes mellitus (IDDM). Animals were divided into 6 groups: groups 1, 3, and 5 were controls consisting of normal, diabetic (streptozotocin-treated, once at 0 time), and diabetic supplemented daily with insulin, respectively, whereas groups 2, 4, and 6 were the controls treated daily with losartan. One month after enrollment, rats were sacrificed and samples of cardiac tissue were snapped frozen for immunostaining and Western blotting. Insulin receptor density was observed to be upregulated in the cardiomyocytes of diabetic animals, but downregulated with insulin supplementation alone. Cotreatment with insulin and an ARB resulted in drastic increase in insulin-receptor density in the diabetic rats. In addition, expression of ETA-R in cardiomyocytes was upregulated and was consistently maintained within the various treatment modalities. However, ETB-R expression was significantly reduced in the diabetic group treated with both insulin and an ARB. The changes in the expression of the insulin, the ETA-Rs, and the ETB-Rs at the various sites of the myocardium and the effect of both insulin treatment and blockade of the AT1-R explain the new benefits related to the halting of myocardial remodeling in IDDM rats.
本项目评估胰岛素和（或）血管紧张素 II 受体 1 型（AT1-R）阻滞剂（ARB）对胰岛素依赖型糖尿病（IDDM）大鼠心脏中胰岛素受体和内皮素-1 受体亚型（ETA-R 和 ETB-R）调节的治疗作用。动物分为 6 组：第 1、3 和 5 组为对照组，分别由正常大鼠、糖尿病大鼠（在 0 时刻一次性注射链脲佐菌素处理）和每日补充胰岛素的糖尿病大鼠组成，而第 2、4 和 6 组为每日用氯沙坦治疗的对照组。入组 1 个月后，处死大鼠，取心脏组织样本速冻用于免疫染色和蛋白质印迹分析。观察到糖尿病动物心肌细胞中胰岛素受体密度上调，但仅补充胰岛素后下调。胰岛素与 ARB 联合治疗导致糖尿病大鼠胰岛素受体密度急剧增加。此外，心肌细胞中 ETA-R 的表达上调，且在各种治疗方式下持续维持。然而，在同时接受胰岛素和 ARB 治疗的糖尿病组中，ETB-R 的表达显著降低。心肌不同部位胰岛素、ETA-R 和 ETB-R 表达的变化以及胰岛素治疗和 AT1-R 阻断的作用解释了与 IDDM 大鼠心肌重塑停止相关的新益处。
