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Oxovanadium compounds are molecules that contain the functional group V=O. These include the vanadate ion (VO43-), and peroxovanadium ions. While researches have shown that vanadate ions may have inhibiting effects on Na+/K+ ATPases of certain plasma membranes, oxovanadium compounds are also shown to have some pharmacologically useful properties as well, including insulin-mimetic properties on some metabolic pathways.

Insulin mimetic properties
In practice, insulin can only be taken by injection, but not orally, as it is not orally active. Hence, the insulin mimetic property that these oxovanadium compounds present draws researchers’ attention. This property may have first been reported by Shechter and Karlish in 1980, where vanadate ions were analyzed. Results shown that, given the vanadate concentration optimized, a maximum activation of 90% of the oxidation of glucose can be achieved, when compared with that of insulin.



In later years, many research papers have determined some other oxovanadium compounds as potent insulin mimics, including the following. In 1992, McNeill et al. claimed that bis(maltolato)oxovanadium(IV) demonstrates insulin-mimetic properties. It is reported to have reduced the level of glucose within 24 hours, which is comparably shorter than 1 to 2 weeks of vanadyl sulfates. Moreover, bis(maltolato)oxovanadium(IV) is observed to be less toxic than vanadyl sulfate. In 1997, Liu et al. also reported that a peroxovanadium compound can also have insulin mimetic properties. 1,10-phenanthroline bisperoxovanadate was found to have the ability to reduce blood glucose levels in the first hour after injection, though still not as effective as insulin.



In vitro, bis(picolinato)oxovanadium(IV) complex has shown an ability to inhibit the release of free fatty acid. The complex, given to a rat orally and by injection, was able to normalize blood glucose level of induced diabetic rats for 30 days. The mechanisms of the oxovanadium insulin mimetic properties are still unknown. Although, the researchers have demonstrated that vanadium compound derivatives can stimulate glucose uptake and glycogen synthesis in vivo. It inhibits two key enzymes of gluconeogenesis pathway: pyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase. It also acts as an activator of the PkB signaling pathway and GSK3-B phosphorylation. Insulin resistance has associated with increased risk of diabetes. Protein tyrosine phosphatase (PTP) is a negative regulator of insulin receptor signaling; type II diabetic patients showed an upregulation of PTP. Bis(maltolato)oxovanadium is a competitive reversible inhibitor of PTP and increases autophosphorylation of insulin receptors, thus the compound enhances the insulin sensitivity.

Pharmaceutical development


Several vanadium salts have been undergoing clinical trials for diabetes treatments. The most common adverse effects of these drugs are causing discomfortness in gastrointestinal tracts and having low efficiency in absorption in the human body. One of the vanadium salts used in clinical trials is bis(ethylmaltolato)oxovanadium(IV) (BEOV). BEOV is reported to have satisfying stability and has less chances of causing discomfort in gastrointestinal tracts. In fact, BEOV has shown nearly no adverse effect during its one-month clinical trial.