In vivo effects of peroxoVanadium (PV) compounds as hypoglycaemic agents

Vanadium is a trace element found in most living systems. It has various biological properties. In the last 10 years numerous reports showed that Vanadium administered orally could improve the metabolic state of diabetic animals. The combination of vanadate and H$ sb2$O$ sb2$ produced the new agents called peroxoVanadium (pV) compounds which exerted more potent insulin mimetic effects by activating the insulin receptor kinase. Their application in the treatment of diabetes could be of great benefit clinically in the future. We demonstrated that long-term oral bpV (phen) (a new pV compound) treatment resulted in a lowering of blood glucose levels, with less toxicity than vanadate in STZ-diabetic rats. bpV(phen) was the first agent other than insulin, that was able to maintain the insulin-deprived diabetic BB rats in good apparent health without ketonuria for 25 days by intraperitoneal injection (IP). Although bpV(phen) was ineffective in reducing glucose levels by IP injection in BB rats, it caused a significant decrease of insulin and C peptide levels and in the insulin dose required to maintain the aglycosuric state of the diabetic BB rats. These observations are consistent with a mechanism of bpV(phen) action at tissue levels. The exploration of the properties of pV compounds may help elucidate both the mechanisms of insulin action and the cause of diabetes, and also may give rise to insulin substitutes which could be orally administered for the treatment of diabetes in the future. However IP injection of bpV (phen) also caused severe toxic side effects. The toxic effects of bpV(phen) included inhibition of food and water intake, acceleration of the onset of diabetes and death. Further studies are required to identify second generation pV compounds with better therapeutic/toxicity ratios and to find ways of delivering pVs orally