title: 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.
abstract: 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.
authors: Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut 11-236, Lebanon.
authors: Shushan B
authors: SB
authors: Artinian
authors: Sawsan M
authors: SM
authors: Al Lafi
authors: Suzan S
authors: SS
authors: Boutary
authors: Khalil M
authors: KM
authors: Bitar
authors: Nadine S
authors: NS
authors: Zwainy
authors: Anwar B
authors: AB
authors: Bikhazi
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D004353:Drug Evaluation, Preclinical; D000077270:Exenatide; D005650:Fumarates / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D000067757:Glucagon-Like Peptide-1 Receptor; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism*; D013311:Streptozocin; D014688:Venoms / Q000494:pharmacology*; D000092502:Renin Inhibitors
chemical_list: D000577:Amides; D000077270:Exenatide; D005650:Fumarates; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D013311:Streptozocin; D014688:Venoms; D000092502:Renin Inhibitors; C000593835:Glp1r protein, rat; C446481:aliskiren