Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart

E. Dale Abel; Helen C Kaulbach; Rong Tian; James C.A Hopkins; John Duffy; Thomas Doetschman; Timo Minnemann; Mary-Ellen Boers; Ed Hadro; Corinna Oberste-Berghaus; William Quist; Bradford B Lowell; Joanne S Ingwall; Barbara B Kahn

doi:10.1172/JCI7605

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Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart

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Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart

E. Dale Abel, Helen C Kaulbach, Rong Tian, James C.A Hopkins, John Duffy, Thomas Doetschman, Timo Minnemann, Mary-Ellen Boers, Ed Hadro, Corinna Oberste-Berghaus, …

The Journal of clinical investigation, Vol.104(12), pp.1703-1714

12/15/1999

DOI: 10.1172/JCI7605

PMCID: PMC409881

PMID: 10606624

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Abstract

Glucose enters the heart via GLUT1 and GLUT4 glucose transporters. GLUT4-deficient mice develop striking cardiac hypertrophy and die prematurely. Whether their cardiac changes are caused primarily by GLUT4 deficiency in cardiomyocytes or by metabolic changes resulting from the absence of GLUT4 in skeletal muscle and adipose tissue is unclear. To determine the role of GLUT4 in the heart we used cre-loxP recombination to generate G4H –/– mice in which GLUT4 expression is abolished in the heart but is present in skeletal muscle and adipose tissue. Life span and serum concentrations of insulin, glucose, FFAs, lactate, and β-hydroxybutyrate were normal. Basal cardiac glucose transport and GLUT1 expression were both increased approximately 3-fold in G4H –/– mice, but insulin-stimulated glucose uptake was abolished. G4H –/– mice develop modest cardiac hypertrophy associated with increased myocyte size and induction of atrial natriuretic and brain natriuretic peptide gene expression in the ventricles. Myocardial fibrosis did not occur. Basal and isoproterenol-stimulated isovolumic contractile performance was preserved. Thus, selective ablation of GLUT4 in the heart initiates a series of events that results in compensated cardiac hypertrophy. J. Clin. Invest. 104 :1703–1714 (1999).

Details

Title: Subtitle: Cardiac hypertrophy with preserved contractile function after selective deletion of GLUT4 from the heart
Creators: E. Dale Abel - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Helen C Kaulbach - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Rong Tian - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
James C.A Hopkins - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
John Duffy - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Thomas Doetschman - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Timo Minnemann - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Mary-Ellen Boers - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Ed Hadro - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Corinna Oberste-Berghaus - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
William Quist - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Bradford B Lowell - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Joanne S Ingwall - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Barbara B Kahn - Division of Endocrinology and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA
Resource Type: Journal article
Publication Details: The Journal of clinical investigation, Vol.104(12), pp.1703-1714
Publisher: American Society for Clinical Investigation
DOI: 10.1172/JCI7605
PMID: 10606624
PMCID: PMC409881
ISSN: 0021-9738
eISSN: 1558-8238
Language: English
Date published: 12/15/1999
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: 9984024550802771

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