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

• Published in: Experimental biology and medicine (Maywood, N.J.) Vol. 237; no. 3; p. 334
• Main Authors: Moberly, Steven P, Berwick, Zachary C, Kohr, Meredith, Svendsen, Mark, Mather, Kieren J, Tune, Johnathan D
• Format: Journal Article
• Language: English
• Published: England 01.03.2012
• Subjects: Animals; Blotting, Western; Cardiac Output - drug effects; Coronary Circulation - drug effects; Coronary Vessels - drug effects; Coronary Vessels - metabolism; Dogs; Glucagon-Like Peptide 1 - administration & dosage; Glucagon-Like Peptide-1 Receptor; Glucose - metabolism; Heart - drug effects; Hemodynamics - drug effects; Hemodynamics - physiology; Immunohistochemistry; Male; Microscopy, Confocal; Myocardial Ischemia - metabolism; Myocardium - metabolism; Receptors, Glucagon - biosynthesis; Stroke Volume - drug effects
• ISSN: 1535-3699
• DOI: 10.1258/ebm.2011.011288

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 pmol/L to 1 nmol/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 pmol/L to 1 nmol/L) did not affect blood pressure, coronary blood flow or myocardial oxygen consumption (MVO(2)); 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 mL/min/g; P < 0.001) and MVO(2) (27 ± 2.3 to 15 ± 2.7 μL O(2)/min/g; P < 0.001). At CPP = 40 mmHg, GLP-1 had no effect on coronary blood flow, MVO(2) 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 nmol/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.