Vanadate as an oral antidiabetic agent

Abstract

Today's need for effective oral glucose lowering agents and the recent advances in the understanding of the molecular mechanisms of insulin action have increased attention to the use of vanadate as an oral euglycaemic agent. Vanadate has metabolic actions like insulin. It is efficacious in rodent models of insulin-dependent diabetes (IDDM) and non-insulin-dependent diabetes (NIDDM). Moreover, recent clinical trials of two to three week duration in human NIDDM and IDDM subjects demonstrated that oral vanadate improved insulin sensitivity in all NIDDM subjects and some IDDM subjects. No major side effects were observed. Although vanadate is a potent protein-tyrosine phosphatase (PTPase) inhibitor, the precise glucose lowering mechanism is debatable since the metal is unstable and it is metabolised by cells. Recently chemists have taken advantage of the complex chemical properties of vanadate and have synthesised a variety of vanadium derivatives that are much more potent than vanadate. Some show in vitro enzyme selectivity against PTPases and some are better absorbed and less toxic. These novel agents have been tested in rodent models and the preliminary data suggest that a potent, less toxic vanadium derivative may find a place in diabetes therapy.