Insulinlike effects of vanadate on hepatic glycogen metabolism in nondiabetic and streptozocin-induced diabetic rats.
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.
Pugazhenthi
S
S
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Khandelwal
R L
RL
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005934:Glucagon / Q000097:blood; D006007:Glycogen-Synthase-D Phosphatase / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D010764:Phosphorylase Kinase / Q000378:metabolism; D010765:Phosphorylase Phosphatase / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014638:Vanadates / Q000494:pharmacology*; D014639:Vanadium / Q000097:blood / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D014639:Vanadium; D014638:Vanadates; D005934:Glucagon; D000410:Alanine Transaminase; D011494:Protein Kinases; D010764:Phosphorylase Kinase; D010765:Phosphorylase Phosphatase; D006007:Glycogen-Synthase-D Phosphatase