title: Role of glucagon-like peptide-1 and its agonists on early prevention of cardiac remodeling in type 1 diabetic rat hearts.
abstract: Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from intestinal L cells upon nutrients ingestion, and is currently used for treating diabetes mellitus. It plays an important role in receptor modulation and cross talk with insulin at the coronary endothelium (CE) and cardiomyocytes (CM) in diabetic type 1 rat heart model. We studied the effects of insulin, GLP-1 analogues (exendin-4), and dipeptidyl peptidase-IV (DPP-IV) inhibitor on GLP-1 cardiac receptor modulation. The binding affinity of GLP-1 to its receptor on CE and CM was calculated using a rat heart perfusion model with [(125)I]-GLP-1(7-36). Tissue samples from the heart were used for immunostaining and Western blot analyses. GLP-1 systemic blood levels were measured using ELISA. GLP-1 binding affinity (τ) increased on the CE (0.33 ± 0.01 vs. 0.25 ± 0.01 min; p < 0.001) and decreased on the CM (0.29 ± 0.02 vs. 0.43 ± 0.02 min; p < 0.001) in the diabetic non-treated rats when compared to normal. There was normalization of τ back to baseline on the CE and CM levels with insulin and DPP-IV inhibitor treatment, respectively. Histological sections and immunofluorescence showed receptor up-regulation in diabetic rats with significant decrease and even normalization with the different treatment strategies. Systemic GLP-1 levels increased after 14 days of diabetes induction (10 ± 3.7 vs. 103 ± 58 pM; p = 0.0005). In conclusion, there is a significant GLP-1 receptor affinity modulation on the CE and CM levels in rats with diabetes type 1, and a cross talk with GLP-1 analogues in early prevention of cardiac remodeling.
authors: Department of Physiology, Diana Tamari Sabbagh/2-44, American University of Beirut, Medical Center, P.O.Box 11-0236, Riad El Solh, Beirut 1107 2020, Lebanon.
authors: Ghinwa M
authors: GM
authors: Barakat
authors: Nuha
authors: N
authors: Nuwayri-Salti
authors: Lina N
authors: LN
authors: Kadi
authors: Khalil M
authors: KM
authors: Bitar
authors: Wael A
authors: WA
authors: Al-Jaroudi
authors: Anwar B
authors: AB
authors: Bikhazi
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D020239:Receptor Cross-Talk; D018027:Receptors, Glucagon / Q000187:drug effects / Q000378:metabolism*; D014688:Venoms / Q000494:pharmacology; D020257:Ventricular Remodeling
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide