Assessment of Glucagon-Like Peptide-1 Analogue and Renin Inhibitor on the Binding and Regulation of GLP-1 Receptor in Type 1 Diabetic Rat Hearts

الملخص EN

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 125I-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.