Journal article
Cardiac Hypertrophy Caused by Peroxisome Proliferator- Activated Receptor-γ Agonist Treatment Occurs Independently of Changes in Myocardial Insulin Signaling
Endocrinology (Philadelphia), Vol.148(12), pp.6047-6053
12/01/2007
DOI: 10.1210/en.2006-1559
PMID: 17823261
Abstract
Peroxisome proliferator-activated receptor (PPAR)-γ ligands are insulin sensitizers, widely used in the treatment of type 2 diabetes. A consistent observation in preclinical species is the development of cardiac hypertrophy after short-term treatment with these agents. The mechanisms for this hypertrophy are incompletely understood. Given the important role of insulin signaling in the regulation of myocardial size, we tested the hypothesis that augmentation of myocardial insulin signaling may play a role in PPAR-γ ligand-induced cardiac hypertrophy. We treated mice with cardiomyocyte-restricted knockout of insulin receptors (CIRKO) and littermate controls (wild type) with 2-(2-(4-phenoxy-2-propylphenoxy) ethyl) indole-5-acetic acid (COOH), which is a non-thiazolidinedione PPAR-γ agonist for 2 wk. Two weeks of COOH treatment increased heart weights by 22% in CIRKO mice and 16% in wild type, and induced similar fold increase in the expression of hypertrophic markers such as α-skeletal actin, brain natriuretic peptide, and atrial natriuretic peptide in CIRKO and wild-type (WT) hearts.COOHtreatment increased plasma volume by 10% in COOH-treated WT and CIRKO mice but did not increase systolic or diastolic blood pressure. Echocardiographic analysis was also consistent with volume overload, as evidenced by increased left ventricular diastolic diameters and cardiac output in COOH-treated CIRKO and WT mice. These data indicate that cardiac hypertrophy after PPAR-γ agonist treatment can occur in the absence of myocardial insulin signaling and is likely secondary to the hemodynamic consequences of plasma volume expansion
Details
- Title: Subtitle
- Cardiac Hypertrophy Caused by Peroxisome Proliferator- Activated Receptor-γ Agonist Treatment Occurs Independently of Changes in Myocardial Insulin Signaling
- Creators
- Sandra Sena - Division of Endocrinology, Metabolism and Diabetes, and Program in Human Molecular Biology and Genetics (S.S., I.R.R., A.R.W., H.A.T., N.W., R.O.P., E.D.A.), University of Utah, School of Medicine, Salt Lake City, Utah 84112Isaac R Rasmussen - Division of Endocrinology, Metabolism and Diabetes, and Program in Human Molecular Biology and Genetics (S.S., I.R.R., A.R.W., H.A.T., N.W., R.O.P., E.D.A.), University of Utah, School of Medicine, Salt Lake City, Utah 84112Adam R Wende - Division of Endocrinology, Metabolism and Diabetes, and Program in Human Molecular Biology and Genetics (S.S., I.R.R., A.R.W., H.A.T., N.W., R.O.P., E.D.A.), University of Utah, School of Medicine, Salt Lake City, Utah 84112Alfred P McQueen - Division of Cardiology (A.P.M., S.E.L.), University of Utah School of Medicine, Salt Lake City, Utah 84132Heather A Theobald - Division of Endocrinology, Metabolism and Diabetes, and Program in Human Molecular Biology and Genetics (S.S., I.R.R., A.R.W., H.A.T., N.W., R.O.P., E.D.A.), University of Utah, School of Medicine, Salt Lake City, Utah 84112Nicole Wilde - Division of Endocrinology, Metabolism and Diabetes, and Program in Human Molecular Biology and Genetics (S.S., I.R.R., A.R.W., H.A.T., N.W., R.O.P., E.D.A.), University of Utah, School of Medicine, Salt Lake City, Utah 84112Renata Oliveira Pereira - University of UtahSheldon E Litwin - Division of Cardiology (A.P.M., S.E.L.), University of Utah School of Medicine, Salt Lake City, Utah 84132Joel P Berger - Department of Metabolic Disorders (J.P.B.), Merck Research Laboratories, Rahway, New Jersey 07065E. Dale Abel - Division of Endocrinology, Metabolism and Diabetes, and Program in Human Molecular Biology and Genetics (S.S., I.R.R., A.R.W., H.A.T., N.W., R.O.P., E.D.A.), University of Utah, School of Medicine, Salt Lake City, Utah 84112
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.148(12), pp.6047-6053
- DOI
- 10.1210/en.2006-1559
- PMID
- 17823261
- ISSN
- 0013-7227
- eISSN
- 1945-7170
- Language
- English
- Date published
- 12/01/2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984025284102771
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