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Lack of beta‐3 adrenergic receptor function in ventricles of ob/ob mice
Author(s) -
Romano Fred D.,
Malicay Margaret,
Goeppinger Heidi,
Sondgeroth Korie,
Wahler Gordon M.,
Smith Jacquelyn M.
Publication year - 2008
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.22.1_supplement.1226.28
Subject(s) - medicine , endocrinology , myocyte , inotrope , downregulation and upregulation , stimulation , agonist , chemistry , antagonist , adrenergic receptor , receptor , nadolol , propranolol , biochemistry , gene
Type 2 diabetes mellitus (T2DM) is associated with ventricular dysfunction. Previous studies have shown that activation of the β 3 ‐adrenergic receptor (β 3 AR) mediates a decrease in ventricular function in rodents. Since the β 3 AR is upregulated in hearts from rats with T1DM, we hypothesized that β 3 AR‐mediated inhibitory mechanisms contribute to the myocardial depression of T2DM. The contractile response (myocyte shortening) to the β 3 AR agonist, CL316243, was determined in ventricular myocytes obtained from 12 to 16 week old ob/ob mice, a model for T2DM, and lean ( +/? ) littermates. Basal shortening was induced by electrical stimulation (0.5Hz). CL316243 (100nM) increased myocyte shortening in lean mice by 17.4%, but had no effect on shortening of myocytes from ob/ob mice. SR59230A (100nM), a β 3 AR antagonist, reduced the effect of CL316243 on shortening in lean myocytes. The β 1 /β 2 AR antagonist, nadolol (10μM) had no effect on CL316243 shortening in lean myocytes, consistent with β 3 AR‐mediated shortening of myocytes. Analysis of β 3 AR mRNA transcripts indicated that mRNA levels were reduced in the ob/ob mouse ventricles as compared to lean. These data suggest that the absence of the β 3 AR positive inotropic response in the ob/ob mouse heart could contribute to the myocardial depression seen in T2DM. Supported by the MWU Master of Biomedical Sciences Program and Office of Research and Sponsored Programs.