Artinian Shushan B, Al Lafi Sawsan M, Boutary Suzan S, Bitar Khalil M, Zwainy Nadine S, Bikhazi Anwar B
Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut 11-236, Lebanon.
Exp Diabetes Res. 2011;2011:489708. doi: 10.1155/2011/489708. Epub 2011 Jun 4.
This study focuses on the effects of long-term renin-angiotensin system suppression and/or incretin mimetic therapies on the regulation and binding affinity of GLP-1 to its receptor in the coronary endothelium (CE) and cardiomyocytes (CMs) of type 1 diabetic male Sprague-Dawley rats. The groups assessed are normal (N), streptozotocin-induced diabetic (D), Insulin treated (DI), Exendin-4 treated (DE), Aliskiren treated (DA), cotreated with Insulin and Aliskiren (DIA) and cotreated with exendin-4 and Aliskiren (DEA). Heart perfusion with (125)I-GLP-1 was performed to estimate GLP-1 binding affinity (τ = 1/k-n) to its receptor in the heart. Western Blotting was assessed to determine the expression variation of GLP-1 receptor in the heart. Plasma GLP-1 levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). Diabetes decreased the τ value on CE and increased it on CMs compared to normal. The combination of Exendin-4 with Aliskiren showed a normalizing effect on the binding affinity of GLP-1 at the coronary endothelium, while at the cardiomyocyte level Exendin-4 treatment alone was the most effective.
本研究聚焦于长期肾素-血管紧张素系统抑制和/或肠促胰岛素类似物疗法对1型糖尿病雄性Sprague-Dawley大鼠冠状动脉内皮（CE）和心肌细胞（CMs）中胰高血糖素样肽-1（GLP-1）对其受体的调节及结合亲和力的影响。所评估的组包括正常组（N）、链脲佐菌素诱导的糖尿病组（D）、胰岛素治疗组（DI）、艾塞那肽-4治疗组（DE）、阿利吉仑治疗组（DA）、胰岛素与阿利吉仑联合治疗组（DIA）以及艾塞那肽-4与阿利吉仑联合治疗组（DEA）。用（125）I-GLP-1进行心脏灌注以评估GLP-1对其在心脏中受体的结合亲和力（τ = 1/k-n）。通过蛋白质免疫印迹法评估以确定心脏中GLP-1受体的表达变化。使用酶联免疫吸附测定（ELISA）测量血浆GLP-1水平。与正常组相比，糖尿病使CE上的τ值降低，而使CMs上的τ值升高。艾塞那肽-4与阿利吉仑联合用药对冠状动脉内皮处GLP-1的结合亲和力具有归一化作用，而在心肌细胞水平，单独使用艾塞那肽-4治疗最为有效。
