A major role of insulin in mammals is the regulation of glucose homeostasis by modulating glucose production in the liver and glucose utilization in other tissues. Liver glucokinase (EC 2.7.1.2) has a key role in glucose metabolism. This enzyme is dependent on insulin for full activity. Failure of the pancreas to produce and secrete an adequate amount of insulin leads to Hyperglycemia and failure of glucose homeostasis.
Current evidences indicate that vanadium compounds could mimic insulin action. Thus it appears that vanadyl sulfate may have an insulin-like effect on liver glucokinase activity. We investigated the effects of oral administration of vanadyl sulfate (0.5mg/ml in drinking water) on hepatic glucokinase activity in nondiabetic and diabetic rats. Male Wistar Methods: rats were randomly divided into four groups of control; vanadyl-treated control; streptozotocin(STZ)- injected; and vanadyl-treated STZ-injected. Animals were made diabetic by intraperitoneal (i.p) injection of STZ(60mg/Kg). Blood glucose level was measured by glucose oxidase-peroxidase method. Blood insulin was determined by the immunoradiometric assay (IRMA). Liver glucokinase activity was calculated from the difference between glucose phosphorylation capacity at 100 and 0.5mM glucose ,using the continuous assay. STZ-induced diabetic animals showed more than four fold increase in blood glucose levels and 83% decrease in blood insulin level. Vanadyl treatment (4 weeks) in diabetic rats lead to a significant decrease (P<0.001) in blood glucose levels, but vanadyl treatment did not significantly alter blood insulin levels in diabetic rats. Although in diabetic animals no significant activity of glucokinase was detected, but vanadyl treatment restored the enzyme activity to about 67.6% of the control value. Treatment of control rats with vanadyl sulfate did not significantly modify glucokinase activity and blood glucose levels, although in vanadyl-treated control group blood insulin level decreased by 58 %. Results obtained from the present study indicated that vanadyl sulfate mimic insulin action in vivo by reducing the high blood glucose level and restoring liver glucokinase activity in diabetic rat. So, one of the mechanism by which vanadyl sulfate restores normoglycemia is probably attributed to the hepatic effect of this compound.