Insulin-like actions of vanadium: potential as a therapeutic agent

Vanadium compounds are glucose-lowering agents that are shown to mimic/enhance most of the metabolic actions of insulin both in vitro and in vivo. Several studies have demonstrated that vanadium treatment lowers plasma glucose levels in experimental models of type 1 diabetes and enhances insulin sensitivity in models of type 2 diabetes. Therefore, these compounds have gained attention as candidates for oral therapy in both types of diabetes. Despite numerous studies, the mechanism(s) by which vana-dium mediates its metabolic effects in vivo are still not completely understood. The finding that most of the insulin-like effects of vanadium in vitro are observed in the presence of high concentrations of vanadium that are not usually achieved in vivo suggests that these effects of vanadium may not have therapeutic relevance. Also, a growing body of evidence from in vivo studies indicates that enhancing glucose dis-posal in the peripheral tissues is not an adequate explanation for the glucose lowering effects of vanadium in vivo. Accordingly, recent studies suggest that suppression of hepatic glucose production through inhibition of key gluconeogenic enzymes might have an important role in mediating the glucoregulatory effects of vanadium. Several potential sites in the insulin-signaling pathways, including both receptor and postre-ceptor mechanisms, have been proposed for the insulin-like effects of vanadium compounds. In this review, we have attempted to discuss the possible molecular mechanism(s) underlying the metabolic effects of vanadium in vivo. J. Trace Elem