Mitochondrial dysfunction accompanies diastolic dysfunction in
diabetic cardiomyopathy.
Flarsheim, Claire E., Ingrid L. Grupp, and Mohammed A. Matlib.
Pharmacology and Cell Biophysics, College of Medicine, University
of Cincinnati, Cincinnati, OH 45267-0575
APStracts 2:0551H, 1995.
The objective of this study was to determine whether a defect in
mitochondrial respiratory function accompanies the development of
diabetic cardiomyopathy. The hypothesis tested in this study is that
a decrease in Ca2+ uptake into mitochondria may prevent the
stimulation of Ca2+-sensitive matrix dehydrogenases and the rate of
ATP synthesis. Streptozotocin(55 mg/kg)-induced diabetic rats were
used as a model of insulin dependent diabetes mellitus. Hearts from
4-week diabetic rats had basal heart rates and rates of contraction
and relaxation similar to control. Isoproterenol caused a similar
increase in the rate of contraction in diabetic and control hearts
whereas the peak rate of relaxation was reduced in diabetic hearts.
Mitochondrial Ca2+ uptake was reduced in mitochondria from diabetic
hearts after 2 weeks of diabetes. Na+-induced Ca2+ release was
unchanged. State 3 respiration rate was depressed in mitochondria
from diabetic rats only when the respiration was supported by the
substrate of a Ca2+-regulated matrix enzyme. The pyruvate
dehydrogenase activity was reduced in diabetic mitochondria compared
to that of control. It was concluded that mitochondria from diabetic
hearts had a decreased capacity to upregulate ATP synthesis via
stimulation of Ca2+ sensitive matrix dehydrogenases. The impairment
in the augmentation of ATP synthesis rate accompanies a decreased
rate of relaxation during increased workload.
Received 27 July 1995; accepted in final form 21 November 1995.
APS Manuscript Number H710-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95