Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy

Circulation. 2004 Aug 24;110(8):955-61. doi: 10.1161/01.CIR.0000139339.85840.DD. Epub 2004 Aug 16.


Background: The failing heart demonstrates a preference for glucose as its metabolic substrate. Whether enhancing myocardial glucose uptake favorably influences left ventricular (LV) contractile performance in heart failure remains uncertain. Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin with potent insulinotropic effects the action of which is attenuated when glucose levels fall below 4 mmol. We examined the impact of recombinant GLP-1 (rGLP-1) on LV and systemic hemodynamics and myocardial substrate uptake in conscious dogs with advanced dilated cardiomyopathy (DCM) as a mechanism for overcoming myocardial insulin resistance and enhancing myocardial glucose uptake.

Methods and results: Thirty-five dogs were instrumented and studied in the fully conscious state. Advanced DCM was induced by 28 days of rapid pacing. Sixteen dogs with advanced DCM received a 48-hour infusion of rGLP-1 (1.5 pmol x kg(-1) x min(-1)). Eight dogs with DCM served as controls and received 48 hours of a saline infusion (3 mL/d). Infusion of rGLP-1 was associated with significant (P<0.02) increases in LV dP/dt (98%), stroke volume (102%), and cardiac output (57%) and significant decreases in LV end-diastolic pressure, heart rate, and systemic vascular resistance. rGLP-1 increased myocardial insulin sensitivity and myocardial glucose uptake. There were no significant changes in the saline control group.

Conclusions: rGLP-1 dramatically improved LV and systemic hemodynamics in conscious dogs with advanced DCM induced by rapid pacing. rGLP-1 has insulinomimetic and glucagonostatic properties, with resultant increases in myocardial glucose uptake. rGLP-1 may be a useful metabolic adjuvant in decompensated heart failure.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Cardiac Pacing, Artificial / adverse effects
  • Cardiomyopathy, Dilated / drug therapy*
  • Cardiomyopathy, Dilated / etiology
  • Cardiomyopathy, Dilated / metabolism
  • Consciousness
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Energy Metabolism / drug effects
  • Fatty Acids / metabolism
  • Female
  • Glucagon / administration & dosage
  • Glucagon / genetics
  • Glucagon / pharmacology
  • Glucagon / therapeutic use*
  • Glucagon-Like Peptide 1
  • Glucose / metabolism*
  • Glucose Clamp Technique
  • Heart Failure / drug therapy*
  • Heart Failure / etiology
  • Heart Failure / metabolism
  • Hemodynamics / drug effects
  • Hyperinsulinism / complications
  • Infusions, Intravenous
  • Insulin Resistance
  • Male
  • Myocardium / metabolism*
  • Oxygen Consumption
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use*
  • Protein Precursors / administration & dosage
  • Protein Precursors / genetics
  • Protein Precursors / pharmacology
  • Protein Precursors / therapeutic use*
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Ventricular Dysfunction, Left / drug therapy*
  • Ventricular Dysfunction, Left / etiology
  • Ventricular Dysfunction, Left / metabolism


  • Blood Glucose
  • Fatty Acids
  • Peptide Fragments
  • Protein Precursors
  • Recombinant Proteins
  • Glucagon-Like Peptide 1
  • Glucagon
  • Glucose