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

Experimental Biology and Medicine
Steven P MoberlyJohnathan D Tune

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 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)/m...Continue Reading

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Citations

Jun 3, 2014·Reviews in Endocrine & Metabolic Disorders·Adam G GoodwillJohnathan D Tune
Jun 10, 2014·Reviews in Endocrine & Metabolic Disorders·Jan HansenMichael Gejl
Jun 15, 2013·Basic Research in Cardiology·Steven P MoberlyJohnathan D Tune
May 6, 2015·Molecular Medicine Reports·Kai LuDongying Zhang
Oct 24, 2014·Cardiovascular Diabetology·Francisco Kerr Saraiva, Andrei C Sposito
Mar 18, 2013·Journal of Diabetes Investigation·Yutaka Seino, Daisuke Yabe
Jul 19, 2018·The Journal of Clinical Endocrinology and Metabolism·Kieren J MatherGary D Hutchins
Oct 13, 2016·Endocrine Reviews·Gemma Pujadas, Daniel J Drucker
Mar 26, 2021·British Journal of Pharmacology·Johanna HelmstädterSebastian Steven

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Methods Mentioned

BETA
confocal microscopy
protein assay

Software Mentioned

Matlab

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