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

Exp Diabetes Res. 2011:2011:489708. doi: 10.1155/2011/489708. Epub 2011 Jun 4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / pharmacology*
  • Animals
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / pathology*
  • Drug Evaluation, Preclinical
  • Exenatide
  • Fumarates / pharmacology*
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glucagon-Like Peptide-1 Receptor
  • Heart / drug effects*
  • Heart / physiology
  • Hypoglycemic Agents / pharmacology
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Peptides / pharmacology*
  • Protein Binding / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucagon / agonists
  • Receptors, Glucagon / metabolism*
  • Renin / antagonists & inhibitors*
  • Streptozocin
  • Venoms / pharmacology*

Substances

  • Amides
  • Fumarates
  • Glp1r protein, rat
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • aliskiren
  • Streptozocin
  • Glucagon-Like Peptide 1
  • Exenatide
  • Renin