THE PROTEIN-TYROSINE-PHOSPHATASE INHIBITOR, PERVANADATE, IS A POWERFUL ANTIDIABETIC AGENT IN STREPTOZOTOCIN-TREATED DIABETIC RATS

The effect of pervanadate, a potent insulinomimetic agent that inhibit s insulin receptor dephosphorylation in vitro, is now assessed in vivo . A single i.p. administration of pervanadate at concentrations as low as 700 mu g vanadium/kg body wt markedly lowered blood glucose levels in streptozotocin-induced diabetic rats from 430 +/- 28 to 212 +/- 30 mg/100 ml within 3 h. A decrease was already observed half hour after treatment, continued in accelerating fashion to the 3rd h, and persis ted for at least 24 h. The initial hyperglycemia reoccurred on the sec ond day and remained thereafter. In comparable fashion, pervanadate de creased the blood glucose levels of control healthy rats, treated iden tically. Within this period body wt was not significantly altered in e ither group. This data indicate that rapid and efficient management of glucose homeostasis is achieved via inhibiting receptor dephosphoryla tion. This observation may lead to a new therapeutic approach of prote in tyrosine phosphatase inhibition for future treatment of diabetes in general, and in insulin resistant states in particular.