Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow

Steven P. Moberly, Zachary C. Berwick, Meredith Kohr, Mark Svendsen, Kieren Mather, Johnathan Tune

Research output: Contribution to journalArticle

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Abstract

We examined the acute dose-dependent effects of intracoronary glucagon-like peptide (GLP)-1 (7-36) on coronary vascular tone, cardiac contractile function and metabolism in normal and ischemic myocardium. Experiments were conducted in open chest, anesthetized dogs at coronary perfusion pressures (CPP) of 100 and 40 mmHg before and during intracoronary GLP-1 (7-36) infusion (10 μmol/L to 1 μmol/L). Isometric tension studies were also conducted in isolated coronary arteries. Cardiac and coronary expression of GLP-1 receptors (GLP-1R) was assessed by Western blot and immunohistochemical analysis. GLP-1R was present in the myocardium and the coronary vasculature. The tension of intact and endothelium-denuded coronary artery rings was unaffected by GLP-1. At normal perfusion pressure (100 mmHg), intracoronary GLP-1 (7-36) (targeting plasma concentration 10 μmol/L to 1 μmol/L) did not affect blood pressure, coronary blood flow or myocardial oxygen consumption (MVO2); however, there were modest reductions in cardiac output and stroke volume. In untreated control hearts, reducing CPP to 40 mmHg produced marked reductions in coronary blood flow (0.50±0.10 to 0.17±0.03 μL/min/g; P, 0.001) and MVO2 (27±2.3 to 15±2.7 μL O2/min/g; P> 0.001). At CPP= 40 mmHg, GLP-1 had no effect on coronary blood flow, MVO2 or regional shortening, but dose-dependently increased myocardial glucose uptake from 0.11±0.02 μmol/min/g at baseline to 0.17±0.04 μmol/min/g at 1 μmol/L GLP-1 (P> 0.001). These data indicate that acute, intracoronary administration of GLP-1 (7-36) preferentially augments glucose metabolism in ischemic myocardium, independent of effects on cardiac contractile function or coronary blood flow.

Original languageEnglish
Pages (from-to)334-342
Number of pages9
JournalExperimental Biology and Medicine
Volume237
Issue number3
DOIs
StatePublished - Mar 2012

Fingerprint

Glucagon-Like Peptide 1
Myocardium
Blood
Perfusion
Pressure
Glucose
Metabolism
Coronary Vessels
Glucagon-Like Peptides
Cardiac Volume
Blood pressure
Oxygen Consumption
Cardiac Output
Stroke Volume
Endothelium
Blood Vessels
Thorax
Western Blotting
Dogs
Oxygen

Keywords

  • Canine
  • Cardiac metabolism
  • Coronary blood flow
  • GLP-1
  • Myocardial oxygen consumption

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Intracoronary glucagon-like peptide 1 preferentially augments glucose uptake in ischemic myocardium independent of changes in coronary flow. / Moberly, Steven P.; Berwick, Zachary C.; Kohr, Meredith; Svendsen, Mark; Mather, Kieren; Tune, Johnathan.

In: Experimental Biology and Medicine, Vol. 237, No. 3, 03.2012, p. 334-342.

Research output: Contribution to journalArticle

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AB - We examined the acute dose-dependent effects of intracoronary glucagon-like peptide (GLP)-1 (7-36) on coronary vascular tone, cardiac contractile function and metabolism in normal and ischemic myocardium. Experiments were conducted in open chest, anesthetized dogs at coronary perfusion pressures (CPP) of 100 and 40 mmHg before and during intracoronary GLP-1 (7-36) infusion (10 μmol/L to 1 μmol/L). Isometric tension studies were also conducted in isolated coronary arteries. Cardiac and coronary expression of GLP-1 receptors (GLP-1R) was assessed by Western blot and immunohistochemical analysis. GLP-1R was present in the myocardium and the coronary vasculature. The tension of intact and endothelium-denuded coronary artery rings was unaffected by GLP-1. At normal perfusion pressure (100 mmHg), intracoronary GLP-1 (7-36) (targeting plasma concentration 10 μmol/L to 1 μmol/L) did not affect blood pressure, coronary blood flow or myocardial oxygen consumption (MVO2); however, there were modest reductions in cardiac output and stroke volume. In untreated control hearts, reducing CPP to 40 mmHg produced marked reductions in coronary blood flow (0.50±0.10 to 0.17±0.03 μL/min/g; P, 0.001) and MVO2 (27±2.3 to 15±2.7 μL O2/min/g; P> 0.001). At CPP= 40 mmHg, GLP-1 had no effect on coronary blood flow, MVO2 or regional shortening, but dose-dependently increased myocardial glucose uptake from 0.11±0.02 μmol/min/g at baseline to 0.17±0.04 μmol/min/g at 1 μmol/L GLP-1 (P> 0.001). These data indicate that acute, intracoronary administration of GLP-1 (7-36) preferentially augments glucose metabolism in ischemic myocardium, independent of effects on cardiac contractile function or coronary blood flow.

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