Aging is associated with myocardial insulin resistance and mitochondrial dysfunction
Siva Bhashyam1, Pratik Parikh, Hakki Bolukoglu
1Department of Medicine, Allegheny General Hospital, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|September 18, 2007
Summary
Aging impairs heart and whole-body insulin sensitivity, independent of weight or activity. This age-related insulin resistance involves mitochondrial changes and reduced cellular insulin action, impacting glucose uptake.
Area of Science:
- Cardiovascular physiology
- Metabolic research
- Aging science
Background:
- Aging is linked to insulin resistance, particularly in skeletal muscle, often due to obesity and inactivity.
- Mitochondrial alterations are implicated in skeletal muscle insulin resistance during aging.
- The impact of aging on myocardial (heart muscle) insulin sensitivity and mitochondrial structure remains largely unknown.
Purpose of the Study:
- To investigate whether aging affects myocardial insulin sensitivity and cellular function.
- To compare insulin sensitivity, glucose uptake, and mitochondrial structure in young versus old dogs.
- To determine the role of mitochondrial alterations in age-related myocardial insulin resistance.
Main Methods:
- Utilized young (4 years) and old (11 years) dogs, matched for body mass, undergoing a standardized exercise program.
- Instrumented dogs for hemodynamic measurements and conducted hyperinsulinemic-euglycemic clamps to assess whole-body and myocardial glucose/fatty acid uptake.
- Analyzed myocardial and skeletal muscle tissue for insulin signaling components, glucose transporter (GLUT4) translocation, and mitochondrial structure, including uncoupling protein-3 expression.
Main Results:
- Old dogs exhibited higher plasma nonesterified fatty acids and insulin levels compared to young dogs.
- Impaired total body glucose disposition and significantly reduced insulin-stimulated myocardial glucose uptake were observed in old dogs.
- Altered insulin signaling, impaired GLUT4 translocation, and myocardial mitochondrial structural changes (decreased uncoupling protein-3) were associated with aging.
Conclusions:
- Aging is associated with both whole-body and myocardial insulin resistance, irrespective of obesity and inactivity.
- Altered mitochondrial structure and impaired cellular insulin action are key features of age-related myocardial insulin resistance.
- These findings highlight mitochondrial dysfunction as a critical factor in the aging heart's response to insulin.
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