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Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice
Ellen Aasum1, Anne D Hafstad, David L Severson
1Department of Medical Physiology, Faculty of Medicine, University of Tromsoe, Norway. ellenaa@fagmed.uit.no
Diabetes
|January 24, 2003
Summary
Diabetic hearts show increased fatty acid use and reduced function over time. This metabolic shift precedes cardiac dysfunction, impacting recovery after ischemia.
Area of Science:
- Cardiovascular Physiology
- Metabolic Disorders
- Diabetic Cardiomyopathy
Background:
- Type 2 diabetes is linked to cardiovascular complications.
- Diabetic cardiomyopathy involves metabolic alterations and impaired cardiac function.
Purpose of the Study:
- To investigate metabolic and functional changes in diabetic mouse hearts.
- To assess the impact of diabetes on cardiac performance and ischemia-reperfusion.
Main Methods:
- Ex vivo perfused working hearts from control (db/+) and diabetic (db/db) mice were used.
- Measurements included glucose and palmitate metabolism and contractile function at various ages.
- Mechanical function after ischemia-reperfusion was examined in male mice.
Main Results:
- Diabetic hearts showed increased palmitate oxidation and decreased carbohydrate oxidation with age.
- Contractile function declined progressively in diabetic hearts.
- Post-ischemic recovery was reduced in diabetic hearts, correlating with age-dependent dysfunction.
Conclusions:
- Diabetic db/db hearts develop progressive cardiomyopathy with altered substrate utilization.
- Increased fatty acid oxidation precedes functional decline and impaired ischemia-reperfusion recovery.
- Peroxisome proliferator-activated receptor-alpha treatment did not improve ischemia-reperfusion sensitivity.