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Intracoronary infusion of Glucagon‐like peptide 1 acutely enhances myocardial glucose uptake during ischemia in canines
Author(s) -
Moberly Steven Paul,
Berwick Zachary C,
Kohr Meredith,
Svendsen Mark,
Mather Kieren J,
Tune Johnathan D
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1097.11
Subject(s) - medicine , perfusion , cardiology , blood flow , ischemia , glucose uptake , artery , glucagon like peptide 1 , coronary perfusion pressure , coronary circulation , coronary arteries , blood pressure , anesthesia , endocrinology , diabetes mellitus , insulin , type 2 diabetes , cardiopulmonary resuscitation , resuscitation
The objective of this study was to examine acute coronary, cardiac and metabolic effects of glucagon‐like peptide 1 (GLP‐1) 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 infusion (10 pM ‐ 1 nM). Isometric tension studies were also conducted in isolated coronary arteries. GLP‐1 did not affect blood pressure, coronary blood flow (CBF), myocardial oxygen consumption (MVO 2 ) or glucose uptake at CPP = 100 mmHg. Tension of intact and denuded coronary artery rings was also unaffected by GLP‐1 (10 pM ‐ 1 nM). At CPP=100 mmHg, GLP‐1 (1 nM) reduced cardiac output (2.5 ± 0.7 to 1.9 ± 0.5 L/min) and reduced regional segment shortening by 27 ± 6%. Reducing CPP to 40 mmHg caused expected decreases in CBF (0.50 ± 0.10 to 0.17 ± 0.03 ml/min/g) and MVO 2 (287 ± 32 to 165 ± 43 □l O 2 /min/g), and regional shortening fell by 70 ± 5%. At CPP=40 mmHg GLP‐1 had no affect on CBF, MVO 2 , or regional shortening, but dose‐dependently increased myocardial glucose uptake (0.09 ± 0.03 to 0.13 ± 0.03 □mol/min/g (sham – 1nM)). These data indicate that GLP‐1 acutely augments glucose metabolism in ischemic myocardium, independent of effects on cardiac contractile function and without altering CBF. These studies suggest GLP‐1 may be of therapeutic value in manipulating myocardial fuel selection during ischemia.