Journal article
Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression
The Journal of clinical investigation, Vol.109(5), pp.629-639
03/01/2002
DOI: 10.1172/JCI13946
PMCID: PMC150890
PMID: 11877471
Abstract
To investigate the role of insulin signaling on postnatal cardiac development, physiology, and cardiac metabolism, we generated mice with a cardiomyocyte-selective insulin receptor knockout (CIRKO) using cre/
loxP
recombination. Hearts of CIRKO mice were reduced in size by 20–30% due to reduced cardiomyocyte size and had persistent expression of the fetal β-myosin heavy chain isoform. In CIRKO hearts, glucose transporter 1 (GLUT1) expression was reduced by about 50%, but there was a twofold increase in GLUT4 expression as well as increased rates of cardiac glucose uptake in vivo and increased glycolysis in isolated working hearts. Fatty acid oxidation rates were diminished as a result of reduced expression of enzymes that catalyze mitochondrial β-oxidation. Although basal rates of glucose oxidation were reduced, insulin unexpectedly stimulated glucose oxidation and glycogenolysis in CIRKO hearts. Cardiac performance in vivo and in isolated hearts was mildly impaired. Thus, insulin signaling plays an important developmental role in regulating postnatal cardiac size, myosin isoform expression, and the switching of cardiac substrate utilization from glucose to fatty acids. Insulin may also modulate cardiac myocyte metabolism through paracrine mechanisms by activating insulin receptors in other cell types within the heart.
Details
- Title: Subtitle
- Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression
- Creators
- Darrell D Belke - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaSandrine Betuing - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaMartin J Tuttle - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaChristophe Graveleau - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaMartin E Young - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaMark Pham - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaDongfang Zhang - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaRobert C Cooksey - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaDonald A McClain - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaSheldon E Litwin - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaHeinrich Taegtmeyer - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaDavid Severson - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaC. Ronald Kahn - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, CanadaE. Dale Abel - Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.109(5), pp.629-639
- DOI
- 10.1172/JCI13946
- PMID
- 11877471
- PMCID
- PMC150890
- NLM abbreviation
- J Clin Invest
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Publisher
- American Society for Clinical Investigation
- Language
- English
- Date published
- 03/01/2002
- 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
- 9984024401402771
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