A new concept: the use of vanadium complexes in the treatment of diabetes mellitus

Abstract

In the 21st century, patients suffering from diabetes mellitus (DM), a lifestyle-related disease, will increase more than in the 20th century. DM is threatening because of the development of many severe secondary complications, including atherosclerosis, microangiopathy, renal dysfunction and failure, cardiac abnormalities, diabetic retinopathy, and ocular disorders. Generally, DM is classified as either insulin-dependent type 1 or noninsulin-dependent type 2 DM. Type 1 DM is treated only by daily insulin injections; type 2 DM is treated by several types of synthetic therapeutic substances together with a controlled diet and physical exercise. Even with these measures, the daily necessity for several insulin injections can be painful both physically and mentally, whereas the synthetic therapeutic substances used over the long term often have side effects. For those reasons, the creation and development of a new class of pharmaceuticals for treatment of DM in the 21st century would be extremely desirable. In the last half of the 20th century, investigations of the relationships among diseases and micronutrients, such as iron, copper, zinc, and selenium, have been numerous. Research into the development of metallopharmaceuticals involving the platinum-containing anticancer drug, cisplatin, and the gold-containing rheumatoid arthritis drug, auranofin, has also been widespread. Such important findings prompted us to develop therapeutic reagents based on a new concept to replace either insulin injections or the use of synthetic drugs. After many trials, we noticed that vanadium might be very useful in the treatment of DM. Before the discovery of insulin by Banting and Best in 1921 and its clinical trial for treating DM, the findings in 1899, in which orally administered sodium vanadate (NaVO(3)) was reported to improve human DM, gave us the idea to use vanadium to treat DM. However, it has taken a long time to obtain a scientific explanation as to why the metal ion exhibits insulin-mimetic or blood-glucose lowering effects in in vitro and in vivo experiments. After investigations from many perspectives involving biochemistry and bioinorganic chemistry, vanadyl sulfate (VOSO(4)) and its complexes with several types of ligands have been proposed as useful for treating DM in experimental diabetic animals. On the basis of a mechanistic study, this article reports on recent progress regarding the development of antidiabetic vanadyl complexes, emphasizing that the vanadyl ion and its complexes are effective not only in treating or relieving both types of DM but also in preventing the onset of DM.