Diabetes, Vol 39, Issue 7 821-827, Copyright © 1990 by American Diabetes Association
Insulinlike effects of vanadate on hepatic glycogen metabolism in nondiabetic and streptozocin-induced diabetic rats
S Pugazhenthi and RL Khandelwal
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
The effect of oral administration of sodium orthovanadate for 5 wk on
hepatic glycogen metabolism was studied in control and streptozocin-induced
diabetic rats. Diabetes caused hyperglycemia (5-fold increase),
hypoinsulinemia (85% decrease), and hyperglucagonemia (4-fold increase).
There were also marked decreases in liver glycogen and activities of
glycogen-metabolizing enzymes in liver. Although vanadate administration in
control animals showed no significant effect on the various parameters
measured except for a 70% decrease in plasma insulin, this treatment in
diabetic rats restored these parameters to near control values. In diabetic
rats, glycogen synthase a and the activity ratio (activity of glycogen
synthase a divided by activity of total glycogen synthase) decreased to 30%
of control levels and were restored to approximately 70-80% of control
values after vanadate administration. A similar pattern was observed for
the activity of synthase phosphatase. The activities of glycogenolytic
enzymes, i.e., phosphorylase (activity of phosphorylase a and activity of
total phosphorylase), phosphorylase kinase, and protein kinase (in presence
or absence of cAMP), were significantly decreased by 40-70% in diabetic
rats. These enzyme activities were recovered to 70-100% of control values
after vanadate treatment. Phosphorylase phosphatase was not altered by
diabetes, but the vanadate treatment of both groups, i.e., control and
diabetic rats, showed a 25% increase in its activity (P less than 0.01). In
conclusion, these results show insulinlike in vivo action of vanadate on
various parameters related to hepatic glycogen metabolism.