Study of the antidiabetic capacity of the VO(dmpp)2 complex

In this work we report biochemical ex vivo studies with a vanadium compound containing a pyridinone ligand, the bis(1,2-dimethyl-3-hydroxy-4-pyridinonate)oxovanadium (IV), V(IV)O(dmpp)(2), which has shown to have promising antidiabetic activity. The experiments were carried out on primary adipocytes of 6-8 week old Wistar rats. Insulin-stimulated glucose uptake studies were performed using a radioactive assay by measuring the (U)-(14)C-glucose taken up by the isolated adipocytes for 30 min. Adipocytes were incubated with and without insulin and in the presence and absence of different concentrations of V(IV)O(dmpp)(2) (100-500 microM) for 45 min. We observed that in a nontoxic concentration, as demonstrated by the Alamar Blue test, V(IV)O(dmpp)(2) significantly increases glucose uptake, in the absence of insulin, by 5-folds higher than basal, and it has a significant inhibitory effect of 78% on free fatty acid release in isolated adipocytes from normal rats. We also demonstrated that it promotes the phosphorylation of Akt1, a key protein in the insulin signaling cascade. These results were compared with those obtained with another vanadium compound reported in the literature, with a similar structure, the bis(maltolato)oxovanadium (IV) (BMOV), which is now in clinical trials. Our ex vivo results clearly indicate that V(IV)O(dmpp)(2) is a good candidate to be a promising drug for the treatment of diabetes and other metabolic disorders.