Albiglutide, a long lasting glucagon-like peptide-1 analog, protects the rat heart against ischemia/reperfusion injury: evidence for improving cardiac metabolic efficiency.

Abstract

BACKGROUND:

The cardioprotective effects of glucagon-like peptide-1 (GLP-1) and analogs have been previously reported. We tested the hypothesis that albiglutide, a novel long half-life analog of GLP-1, may protect the heart against I/R injury by increasing carbohydrate utilization and improving cardiac energetic efficiency.

METHODS/PRINCIPAL FINDINGS:

Sprague-Dawley rats were treated with albiglutide and subjected to 30 min myocardial ischemia followed by 24 h reperfusion. Left ventricle infarct size, hemodynamics, function and energetics were determined. In addition, cardiac glucose disposal, carbohydrate metabolism and metabolic gene expression were assessed. Albiglutide significantly reduced infarct size and concomitantly improved post-ischemic hemodynamics, cardiac function and energetic parameters. Albiglutide markedly increased both in vivo and ex vivo cardiac glucose uptake while reducing lactate efflux. Analysis of metabolic substrate utilization directly in the heart showed that albiglutide increased the relative carbohydrate versus fat oxidation which in part was due to an increase in both glucose and lactate oxidation. Metabolic gene expression analysis indicated upregulation of key glucose metabolism genes in the non-ischemic myocardium by albiglutide.

CONCLUSION/SIGNIFICANCE:

Albiglutide reduced myocardial infarct size and improved cardiac function and energetics following myocardial I/R injury. The observed benefits were associated with enhanced myocardial glucose uptake and a shift toward a more energetically favorable substrate metabolism by increasing both glucose and lactate oxidation. These findings suggest that albiglutide may have direct therapeutic potential for improving cardiac energetics and function.

• Authors: Weike Bao, Karpagam Aravindhan, Hasan Alsaid, Thimmaiah Chendrimada, Matthew Szapacs, David R Citerone, Mark R Harpel, Robert N Willette, John J Lepore, Beat M Jucker
• Journal: PloS one (PLoS One) Vol. 6 Issue 8 Pg. e23570 ( 2011) ISSN: 1932-6203 [Electronic] United States
• PMID: 21887274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Cardiotonic Agents
• Insulin
• Lactic Acid
• rGLP-1 protein
• Glucagon-Like Peptide 1
• Cyclic AMP

Topics

• Animals
• Blood Glucose (metabolism)
• Body Weight (drug effects)
• Cardiotonic Agents (pharmacology)
• Cyclic AMP (metabolism)
• Energy Metabolism (drug effects)
• Feeding Behavior (drug effects)
• Glucagon-Like Peptide 1 (administration & dosage, analogs & derivatives, blood, pharmacology)
• Heart
• Heart Function Tests
• Hemodynamics (drug effects)
• In Vitro Techniques
• Insulin (blood)
• Lactic Acid (blood)
• Male
• Metabolic Networks and Pathways (drug effects, genetics)
• Myocardial Infarction (complications, pathology, physiopathology)
• Myocardial Reperfusion Injury (complications, physiopathology, prevention & control)
• Myocardium (metabolism)
• Principal Component Analysis
• Rats
• Rats, Sprague-Dawley
• Transcription, Genetic (drug effects)