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

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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

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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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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: Aasum, Ellen
Hafstad, Anne D.
Larsen, Terje S.
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 › Cardiology and Cardiovascular 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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Age-Dependent Changes in Metabolism, Contractile Function, and Ischemic Sensitivity in Hearts From db/db Mice

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