Cited by 99Peroxisome Proliferator-Activated ReceptorsCardiovascular Function and Risk FactorsCardiovascular Disease and Adiposity

Activation of PPARγ enhances myocardial glucose oxidation and improves contractile function in isolated working hearts of ZDF rats

Golfman, Leonard S., Wilson, Christopher R., Sharma, Saumya, Burgmaier, Mathias, Young, Martin E., Guthrie, Patrick H., Van Arsdall, Melissa, Adrogue, Julia V. +2 more·2005·American Journal of Physiology-Endocrinology and Metabolism

Abstract

It is suggested that insulin resistance and metabolic maladaptation of the heart are causes of contractile dysfunction. We tested the hypothesis whether systemic PPARγ activation, by changing the metabolic profile in a model of insulin resistance and type 2 diabetes (the ZDF rat) in vivo, improves contractile function of the heart in vitro. Male Zucker diabetic fatty (ZDF) and Zucker lean (ZL) rats, at 53–56 days of age, were treated with either GI-262570 (a nonthiazolidinedione PPARγ agonist; A) or vehicle (V) for 1 wk. Agonist treatment resulted in correction of hyperglycemia and dyslipidemia, as well as in reduced hyperinsulinemia. The accumulation of triacylglycerols in the myocardium, characteristic of the ZDF rat, disappeared with treatment. Cardiac power and rates of glucose oxidation in the isolated working heart were significantly reduced in ZDF-V rats, but both parameters increased to nondiabetic levels with agonist treatment. In ZDF-V hearts, transcript levels of PPARα-regulated genes and of myosin heavy chain-β were upregulated, whereas GLUT4 was downregulated compared with ZL. Agonist treatment of ZDF rats reduced PPARα-regulated genes and increased transcripts of GLUT4 and GLUT1. In conclusion, by changing the metabolic profile, reducing myocardial lipid accumulation, and promoting the downregulation of PPARα-regulated genes, PPARγ activation leads to an increased capacity of the myocardium to oxidize glucose and to a tighter coupling of oxidative metabolism and contraction in the setting of insulin resistance and type 2 diabetes.

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Crossref · 10.1152/ajpendo.00055.2005

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  • Treatment of Zucker rats with a TZD improved systemic glucose homeostasis and intracardiac triglyceride accumulation, increased glucose oxidation rates, and improved cardiac function.

    “Treatment of Zucker rats with a TZD improved systemic glucose homeostasis and intracardiac triglyceride accumulation, increased glucose oxidation rates, and improved cardiac function (115).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [115]

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Authors
Golfman, L. S., Wilson, C. R., Sharma, S., Burgmaier, M., Young, M. E., Guthrie, P. H., Van Arsdall, M., Adrogue, J. V., Brown, K. K., & Taegtmeyer, H.
Affiliations
  • The University of Texas Health Science Center at Houston (US)
  • GlaxoSmithKline (United Kingdom) (GB)
Venue
American Journal of Physiology-Endocrinology and Metabolism
Published
2005-08
Volume
289
Issue
2
Pages
E328-E336
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
OpenAlex
W2133874700
Cited by
99
References
56
Citations by year
2025: 1 · 2022: 3 · 2021: 5 · 2020: 1 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 6 · 2014: 5 · 2013: 2 · 2012: 10
FWCI
3.76
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • GlaxoSmithKline
  • Studienstiftung des Deutschen Volkes
  • National Heart, Lung, and Blood Institute (R01-HL-43133, R01-HL-73162, T32HL007591, R01HL073162, T32-HL 07591, R01HL043133)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
Keywords
PPARγ activation, cardiac contractile function, insulin resistance, type 2 diabetes, Zucker diabetic fatty rats, GLUT4, GLUT1, beta-myosin heavy chain, hyperinsulinemia, hyperglycemia, dyslipidemia, myocardial metabolism
MeSH terms
Adaptation, Physiological, Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Energy Metabolism, Gene Expression Regulation, Glucose, Insulin Resistance, Male, Myocardial Contraction, Myocardium, Oxazoles, Rats, Inbred Strains, Rats, Zucker, Triglycerides, Tyrosine, Signal Transduction, Transcriptional Activation, PPAR gamma, Rats, In Vitro Techniques

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