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Modulation of Cardiac Metabolism by Beta‐Blockers During Diabetes: A Role in Apoptosis Signaling
Author(s) -
Saran Varun V V,
Sharma Vijay,
Yuen Violet,
Allard Michael F,
McNeill John H
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb411
Subject(s) - diabetic cardiomyopathy , carvedilol , oxidative stress , diabetes mellitus , apoptosis , medicine , endocrinology , streptozotocin , metoprolol , ex vivo , type 2 diabetes , pharmacology , in vivo , heart failure , cardiomyopathy , chemistry , biology , biochemistry , microbiology and biotechnology
Diabetic Cardiomyopathy is characterized by problems during diastole, this is due to loss of contractile tissue after apoptosis. Apoptosis may be caused by increases in oxidative stress associated with metabolic modifications. Beta‐adrenergic receptor antagonists, (β‐blockers) improve heart function. Metoprolol (met) and carvedilol (car) are clinically important β‐blockers that modulate metabolism and reduce apoptosis, car, also has antioxidant properties. We tested whether β‐blockers will reduce apoptosis and improve heart function via oxidative stress dependant and or independent pathways. We employed a Streptozotocin (STZ) induced rat model of type 1 diabetes. This model has been shown to develop diastolic dysfunction. STZ was delivered at 60mg/kg body weight. Met and car were delivered at a rate of 15 and 10mg/kg/day respectively. In order to assess the significance of car's antioxidant abilities, we included groups where met treatment was supplemented with vitamin C at 1000mg/kg/day. Analysis indicates induction of diabetes in STZ animals. β‐blocker treatment caused a significant reduction in heart rates. Remaining analysis includes assessment of in vivo and ex vivo heart function, metabolic flux, apoptosis, expression analysis of effecter proteins involved in apoptosis, and measurement of oxidative stress. Funding for this research was provided by the Canadian Institutes of Health Research