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(Received for publication, May 11, 1995; and in revised form, July 24, 1995) We have previously observed that the chronic effects of
streptozotocin-induced diabetes cause a decrease in the total hepatic
glycogen phosphorylase activity with a corresponding reduction in the
phosphorylase protein levels. These effects were normalized by insulin
administration to diabetic rats. There was no change in the total
glycogen synthase activity as a result of diabetes or insulin
supplementation. These results are extended to examine the effects of
diabetes and insulin administration to diabetic animals on the
expression of phosphorylase and glycogen synthase enzymes. The
expression (i.e. mRNA levels) of phosphorylase was
down-regulated (45% of normal levels) in diabetic livers, and this was
normalized by insulin supplementation to diabetic animals. Diabetes or
insulin supplementation to diabetic rats showed no effect on the
transcription rate of phosphorylase. As expected, diabetes (or insulin
administration to diabetic animals) did not cause any alteration in the
mRNA levels or in the transcription rate of hepatic glycogen synthase.
The stability of phosphorylase mRNA was then examined using hepatocytes
prepared from normal and diabetic rats. Diabetes caused a decrease in
the half-life of phosphorylase mRNA from 14 h in normal hepatocytes to
6.5 h in diabetic hepatocytes. Insulin supplementation to the medium of
diabetic hepatocytes increased the half-life of phosphorylase mRNA to a
level comparable with normal values. This study indicates that the
chronic effect of insulin on the activation of the total hepatic
phosphorylase activity (and protein) is mediated through the
stabilization of its mRNA levels.
Volume 270,
Number 42,
Issue of October 20, 1995 pp. 24955-24960
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
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