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), VIVO(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)–14C–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 VIVO(dmpp)2 (100–500 μM) for 45 min. We observed that in a nontoxic concentration, as demonstrated by the Alamar Blue test, VIVO(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 VIVO(dmpp)2 is a good candidate to be a promising drug for the treatment of diabetes and other metabolic disorders.

The vanadium compound bis(1,2-dimethyl-3-hydroxy-4pyridinonate)oxovanadium(IV), VIVO(dmpp)2, has shown, through ex vivo studies with isolated adipoytes, to have promising antidiabetic activity.Figure optionsDownload as PowerPoint slide