AJP - Endocrinology and Metabolism, Vol 263, Issue 3 E425-E429, Copyright © 1992 by American Physiological Society
Abnormalities in cardiac alpha 1-adrenoceptor and its signal transduction in streptozocin-induced diabetic rats
Y. Tanaka, A. Kashiwagi, Y. Saeki and Y. Shigeta
Third Department of Medicine, Shiga University of Medical Science, Japan.
To investigate a mechanism of diabetic cardiomyopathy, we examined an
alteration of cardiac alpha 1-adrenoceptor (alpha 1-AR) signaling in
streptozotocin-induced diabetic rats. In diabetes, the cell surface alpha
1-AR concentration on isolated cardiac myocytes decreased by 45% without
any change in the dissociation constant, and, moreover, norepinephrine
(NE)-stimulated ventricular inositol 1,4,5-trisphosphate (IP3) production
was also decreased by 34%. In contrast, basal ventricular protein kinase C
(PKC) activity was elevated in both cytosolic (by 98%) and membrane (by
41%) fractions in diabetes. All of these abnormalities seen in diabetes
were reversed by chronic insulin treatment. Rapid activation of PKC by
phorbol ester in the normal rat heart revealed decreases in both receptor
number (by 19%) and NE-stimulated IP3 production (by 21%). These results
indicate that the impairment of cardiac alpha 1-AR signaling is closely
associated with the diabetic state and may be linked, at least in part,
with the abnormal activation of cardiac PKC.
