title: Glucagon-like peptide-1 (GLP-1), immediately prior to reperfusion, decreases neutrophil activation and reduces myocardial infarct size in rodents.
abstract: Glucagon-like peptide-1 (GLP-1) is an incretin that has glucoregulatory effects as well as protective effects in a variety of tissues, including the heart. We hypothesized that GLP-1 may have a direct effect on neutrophils (PMNs) after myocardial ischemia, to ameliorate reperfusion injury. Deeply anesthetized Sprague-Dawley rats underwent 30 min of left coronary artery occlusion followed by 120 min of reperfusion. Immediately prior to reperfusion, rats were treated with either GLP-1 (human rGLP-1, 30 pM/kg/min) or PBS as placebo. GLP-1 significantly decreased myocardial infarct size [73.2±11.7% INF/AAR in PBS (n=4) vs. 15.7 ±5.52% INF/AAR in GLP-1-treated animals (n=5),  p<0.05], PMN activation in blood in vivo (fMLP-stimulated CD11b surface expression: PBS 2.78±1.14 vs. GLP-1 1.7±0.21, TFI, p<0.05), and accumulation in myocardium (PBS: 6.52±0.31 vs. GLP-1: 4.78±0.90, n=4-6 animals/group, p<0.05). In addition, we found that GLP-1 mitigated PMN CD11b surface expression in whole rat blood in vitro, an effect that was abolished by GLP-1 receptor blockade (PBS 6.52±0.31 vs. GLP-1 4.78±0.90, TFI, p<0.05). These findings suggest that one mechanism by which GLP-1 decreases reperfusion injury may be the attenuation of PMN-mediated reperfusion injury.
authors.affiliation: Department of Medicine, University of Arizona, Tuscon, USA. bdokken@deptofmed.arizona.edu
authors.forename: B B
authors.initials: BB
authors.lastname: Dokken
authors.forename: L R
authors.initials: LR
authors.lastname: La Bonte
authors.forename: G
authors.initials: G
authors.lastname: Davis-Gorman
authors.forename: M K
authors.initials: MK
authors.lastname: Teachey
authors.forename: N
authors.initials: N
authors.lastname: Seaver
authors.forename: P F
authors.initials: PF
authors.lastname: McDonagh
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D052216:Glucagon-Like Peptide 1 / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000276:immunology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology*; D018375:Neutrophil Activation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D052216:Glucagon-Like Peptide 1