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Cardiac responses to intravenous glucagon‐like peptide 1 are impaired in metabolic syndrome
Author(s) -
Moberly Steven,
Berwick Zachary,
Kohr Meredith,
Mather Kieren,
Tune Johnathan
Publication year - 2012
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.26.1_supplement.1057.11
Subject(s) - medicine , endocrinology , stimulation , heart rate , metabolic syndrome , hemodynamics , glucagon like peptide 1 , blood flow , in vivo , blood pressure , diabetes mellitus , type 2 diabetes , biology , microbiology and biotechnology
The objective of this study was to determine whether intravenous administration of glucagon‐like peptide 1 (GLP‐1) differentially affects hemodynamic and cardiometabolic responses to exercise in lean and metabolic syndrome (MetS) swine. Experiments were conducted in chronically instrumented Ossabaw swine at rest and during graded treadmill exercise with and without a 2 hr systemic infusion of GLP‐1 (7–36) at 1.5 pmol/kg/min. GLP‐1 did not affect blood pressure, heart rate, or myocardial oxygen consumption (MVO 2 ) at rest or during exercise. In lean swine GLP‐1 increased coronary blood flow at all levels of MVO 2 ( P = 0.003), and also increased the slope of the relationship between myocardial glucose uptake and MVO 2 ( P = 0.05). These effects of GLP‐1 were absent in MetS swine. Western blotting and immunohistochemistry demonstrated no differences in expression of the GLP‐1 receptor between lean and MetS swine in coronary ( P = 0.95) or cardiac ( P = 0.46) tissue. In vitro studies using myocardial tissue slices revealed that GLP‐1 (1 to 5 nM) dose dependently increased p38 MAPK activity in lean (P =0.05) but not MetS ( P = 0.5) swine, and did not affect PKA activity in either group. These data indicate that the impaired in‐vivo responses to GLP‐1 in MetS are not due to altered GLP‐1 receptor content or PKA activity, but may involve reduced GLP‐1 stimulation of p38 MAPK. Support: NIH HL092245 and HL092799