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1 Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada; 2 Aoto Hospital, Department of Internal Medicine, Jikei University, Tokyo 125, Japan; and 3 Institute of Biochemistry, University of Perugia, 06100 Perugia, Italy
To understand
cardiac dysfunction in diabetes, the activity of protein kinase C (PKC)
and protein contents of its isozymes (PKC-
, -
, -
, and -
)
were examined in diabetic rats upon injection of streptozotocin (65 mg/kg iv). The hearts were removed at 1, 2, 4, and 8 wk, and some of
the 6-wk diabetic animals had been injected with insulin (3 U/day) for
2 wk. The Ca2+-dependent PKC
activity was increased by 43 and 51% in the homogenate fraction and 31 and 70% in the cytosolic fraction from the 4- and 8-wk diabetic
hearts, respectively, in comparison with control values. The
Ca2+-independent PKC activity was
increased by 24 and 32% in the homogenate fraction and 52 and 89% in
the cytosolic fraction from the 4- and 8-wk diabetic hearts,
respectively, in comparison with control values. The relative protein
contents of PKC-
, -
, -
, and -
isozymes were increased by
43, 31, 48, and 38%, respectively, in the homogenate fraction and by
126, 119, 148, and 129%, respectively, in the cytosolic fraction of
the 8-wk diabetic heart. The observed changes in heart homogenate and
cytosolic fractions were partially reversible upon treatment of the
diabetic rats with insulin. The results suggest that the increased
myocardial PKC activity and increased protein contents of the cytosolic
PKC isozymes are associated with subcellular alterations and cardiac
dysfunction in the diabetic heart.
diabetic cardiomyopathy; diabetic heart dysfunction
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