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 inhibits insulin receptor dephosphorylation in vitro, is now assessed in vivo. A single i.p. administration of pervanadate at concentrations as low as 700 micrograms 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 persisted for at least 24 h. The initial hyperglycemia reoccurred on the second day and remained thereafter. In comparable fashion, pervanadate decreased the blood glucose levels of control healthy rats, treated identically. Within this period body wt was not significantly altered in either group. This data indicate that rapid and efficient management of glucose homeostasis is achieved via inhibiting receptor dephosphorylation. This observation may lead to a new therapeutic approach of protein tyrosine phosphatase inhibition for future treatment of diabetes in general, and in insulin resistant states in particular.
Shisheva
A
A
Department of Hormone Research, Weizmann Institute of Science, Rehovot, Israel.
Ikonomov
O
O
Shechter
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D009994:Osmolar Concentration; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014638:Vanadates / Q000627:therapeutic use*
D001786:Blood Glucose; C076715:pervanadate; D014638:Vanadates; D017027:Protein Tyrosine Phosphatases