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Cited by 94Peroxisome Proliferator-Activated ReceptorsCardiovascular Function and Risk FactorsDiabetes Treatment and Management

Treatment of type 2 diabetic db/db mice with a novel PPARγ agonist improves cardiac metabolism but not contractile function

Carley, Andrew N., Semeniuk, Lisa M., Shimoni, Yakhin, Aasum, Ellen, Larsen, Terje S., Berger, Joel P., Severson, David L.·2004·American Journal of Physiology-Endocrinology and Metabolism
DOI 10.1152/ajpendo.00329.2003
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Abstract

Hearts from insulin-resistant type 2 diabetic db/db mice exhibit features of a diabetic cardiomyopathy with altered metabolism of exogenous substrates and reduced contractile performance. Therefore, the effect of chronic oral administration of 2-(2-(4-phenoxy-2-propylphenoxy)ethyl)indole-5-acetic acid (COOH), a novel ligand for peroxisome proliferator-activated receptor-γ that produces insulin sensitization, to db/db mice (30 mg/kg for 6 wk) on cardiac function was assessed. COOH treatment reduced blood glucose from 27 mM in untreated db/db mice to a normal level of 10 mM. Insulin-stimulated glucose uptake was enhanced in cardiomyocytes from COOH-treated db/db hearts. Working perfused hearts from COOH-treated db/db mice demonstrated metabolic changes with enhanced glucose oxidation and decreased palmitate oxidation. However, COOH treatment did not improve contractile performance assessed with ex vivo perfused hearts and in vivo by echocardiography. The reduced outward K+currents in diabetic cardiomyocytes were still attenuated after COOH. Metabolic changes in COOH-treated db/db hearts are most likely indirect, secondary to changes in supply of exogenous substrates in vivo and insulin sensitization.

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Crossref · 10.1152/ajpendo.00329.2003

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  • Treatment of db/db mice with PPAR-γ or PPAR-α agonists can improve cardiac metabolism, but do not necessarily restore cardiac function.

    “Similar studies in db/db mice revealed that treatment of these mice with PPAR-γ or PPAR-α agonists can improve cardiac metabolism, but do not necessarily restore cardiac function (1, 2, 36).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [36]

  • Treatment with PPAR-γ or PPAR-α agonists while improving myocardial substrate utilization did not increase postischemic recovery in db/db hearts, but acute treatment with high concentrations of glucose and insulin increased postischemic recovery and cardiac efficiency.

    “Treatment with PPAR-γ or PPAR-α agonists while improving myocardial substrate utilization did not increase postischemic recovery in db/db hearts (3, 36), but acute treatment with high concentrations of glucose and insulin, which substantially increased glucose oxidation rates, increased postischemic recovery and cardiac efficiency (90).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [36]

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Authors
Carley, A. N., Semeniuk, L. M., Shimoni, Y., Aasum, E., Larsen, T. S., Berger, J. P., & Severson, D. L.
Affiliations
University of Calgary (CA)
ORCID
Venue
American Journal of Physiology-Endocrinology and Metabolism
Publisher
American Physiological Society
Published
2004-03
Volume
286
Issue
3
Pages
E449-E455
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
DOI
10.1152/ajpendo.00329.2003
OpenAlex
W2059844165
Cited by
94
References
55
Citations by year
2024: 1 · 2023: 1 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 5
FWCI
4.26
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Diabetes Association
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 › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
type 2 diabetes, diabetic cardiomyopathy, PPARγ agonists, db/db mice, insulin resistance, myocardial metabolism, insulin sensitization, glucose uptake, glucose oxidation, palmitate oxidation, cardiac contractile function, cardiomyocytes
MeSH terms
Acetates, Administration, Oral, Animals, Blood Glucose, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Echocardiography, Heart, Indoles, Male, Mice, Inbred C57BL, Myocardial Contraction, Cardiomyopathies, Myocardium, Receptors, Cell Surface, Transcription Factors, Treatment Outcome, Receptors, Cytoplasmic and Nuclear, Mice, Receptors, Leptin

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