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Cited by 280Cardiovascular Function and Risk FactorsCardiac Ischemia and ReperfusionCardiac Fibrosis and Remodeling

Age-Dependent Changes in Metabolism, Contractile Function, and Ischemic Sensitivity in Hearts From db/db Mice

Aasum, Ellen, Hafstad, Anne D., Severson, David L., Larsen, Terje S.·2003·Diabetes
DOI 10.2337/diabetes.52.2.434
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Abstract

Glucose and palmitate metabolism and contractile function were measured with ex vivo perfused working hearts from control (db/+) and diabetic (db/db) female mice at 6, 10–12, and 16–18 weeks of age. Palmitate oxidation was increased by 2.2-fold in 6-week-old db/db hearts and remained elevated in 10- to 12- and 16- to 18-week-old hearts. Carbohydrate oxidation was normal at 6 weeks but was reduced to 27 and 23% of control at 10–12 and 16–18 weeks, respectively. At 6 weeks, db/db hearts exhibited a slight reduction in mechanical function, whereas marked signs of dysfunction were evident at 10–12 and 16–18 weeks. Mechanical function after ischemia-reperfusion was examined in hearts from male mice; at 6 weeks, db/db hearts showed normal recovery, whereas at 12 weeks it was markedly reduced. Fatty acid oxidation was the predominant substrate used after reperfusion. Thus, diabetic db/db hearts exhibit signs of a progressive cardiomyopathy; increased fatty acid oxidation preceded reductions in carbohydrate oxidation. Postischemic recovery of function was reduced in db/db hearts, in parallel with age-dependent changes in normoxic contractile performance. Finally, peroxisome proliferator-activated receptor-α treatment (3 weeks) did not affect sensitivity to ischemia-reperfusion, even though carbohydrate oxidation was increased and palmitate oxidation was decreased.

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  • Isolated working hearts from db/db mice exhibit reduced recovery following ischemia and reperfusion after diabetes develops, but recovery is normal in the pre-diabetic stage.

    “Thus isolated working hearts from db/db mice exhibit reduced recovery following ischemia and reperfusion after diabetes develops, but recovery is normal in the pre-diabetic stage (3).”

    From Cardiac remodeling in obesity (2008) · cites this paper as [3]

  • 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 [3]

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Authors
Aasum, E., Hafstad, A. D., Severson, D. L., & Larsen, T. S.
Affiliations
  • UiT The Arctic University of Norway (NO)
  • University of Calgary (CA)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2003-02-01
Volume
52
Issue
2
Pages
434-441
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.52.2.434
OpenAlex
W2150336836
Cited by
280
References
53
Citations by year
2026: 3 · 2025: 10 · 2024: 10 · 2023: 7 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 12 · 2017: 10 · 2016: 6 · 2015: 17 · 2014: 13 · 2013: 10 · 2012: 21
FWCI
10.56
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Norges Forskningsråd
  • Canadian Institutes of Health Research
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
db/db mice, type 2 diabetes, diabetic cardiomyopathy, myocardial metabolism, palmitate oxidation, fatty acid oxidation, carbohydrate oxidation, cardiac contractile function, ischemia-reperfusion injury, age-related changes, PPARα
MeSH terms
Aging, Animals, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Heart, Hemodynamics, Insulin, Mice, Inbred C57BL, Mice, Mutant Strains, Myocardial Contraction, Myocardium, Organ Size, Oxidation-Reduction, Myocardial Ischemia, Carbohydrate Metabolism, Mice, In Vitro Techniques

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