Effects of peroxovanadate complexes on reducing glycemia in diabetic rats and translocation of glucose transporter

Abstract

Objective: To demonstrate the hypoglycemic effects and translocation of glucose transporter (Glut 1 and Glut 4) promoted by peroxovanadate and nicotinic acid complexes (nicotinic chelated bitriperoxovanadate, POR; N-O nicotinic chelated peroxovanadate, POV) in streptozotozin-induced diabetic rats.

Methods: Peroxovanadate complexes of nicotinic acid (POR and POV) were prepared and characterized in laboratory. POR, POV and vanadate were administrated in drink water. The muscles from diabetic rats were subjected to prepare plasma membrane and microsome membrane. Antibodies to COOH-terminal of glucose transporter were used in Western Blot to evaluate the translocation.

Results: POR and POV showed markedly hypoglycemic effects in streptozotocin (STZ)-induced diabetic rats. POV, which may be a N-oxide compound of peroxovanadate, have high potency of acute effects comparing to carboxylate-complexes of peroxovanadate (POR). In chronic tests, 1 mg/kg oral pathway POR could significantly reduce the plasma glucose levels over four week's treatment, whereas the same dose of single sodium vanadate or nicotinic acid did not have hypoglycemic effects. The net vanadium intake is about 1/90 of single effectively vanadate treatment. The Western Blot showed that POR increased the translocation of Glut 4 and Glut 1 from intracellular site of membrane.

Conclusions: Peroxovanadate-nicotinic acid complexes (POR and POV) are the novel vanadyl that acutely and markedly reduce plasma glucose in a lower dose comparing to vanadate in STZ-DM rats by oral administration. Translocation of glucose transportor may take a part in their hypoglycemic effects.