Role of glucagon-like peptide-1 and its agonists on early prevention of cardiac remodeling in type 1 diabetic rat hearts

Ghinwa M. Barakat, Nuha Nuwayri-Salti, Lina N. Kadi, Khalil M. Bitar, Wael A. Al-Jaroudi, Anwar B. Bikhazi

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

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 [ 125I]-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.

Original languageEnglish (US)
Pages (from-to)34-44
Number of pages11
JournalGeneral Physiology and Biophysics
Volume30
Issue number1
DOIs
StatePublished - Mar 2011
Externally publishedYes

Keywords

  • Binding affinity
  • Dipeptidyl peptidase-IV inhibitor
  • Dissociation constant
  • Exendin-4
  • Glucagon-like peptide-1

ASJC Scopus subject areas

  • Biophysics
  • Physiology

Fingerprint Dive into the research topics of 'Role of glucagon-like peptide-1 and its agonists on early prevention of cardiac remodeling in type 1 diabetic rat hearts'. Together they form a unique fingerprint.

Cite this