Insulin-like effects of vanadium: basic and clinical implications

Most mammalian cells contain vanadium at a concentration of about 20 nM, th e bulk of which is probably in the reduced vanadyl (+ 4) form. Although thi s trace element is essential and should be present in the diet in minute qu antities, no known physiological role for vanadium has been found thus far. In the late 1970s the vanadate ion was shown to act as an efficient inhibi tor of Na+, K+-ATPase as well as of other related phosphohydrolases. In 198 0 vanadium was reported to mimic the metabolic effects of insulin in rat ad ipocytes. During the last decade, vanadium has been found to act in an insu lin-like manner in all three main target tissues of the hormone, namely ske letal muscles, adipose, and liver. Subsequent studies revealed that the act ion of vanadium salts is mediated through insulin-receptor independent alte rnative pathway(s). The investigation of the antidiabetic potency of vanadi um soon ensued. Vanadium therapy was shown to normalize blood glucose level s in STZ-rats and to cure many hyperglycemia-related deficiencies. Therapeu tic effects of vanadium were then demonstrated in type II diabetic rodents, which do not respond to exogenously administered insulin. Finally, clinica l studies indicated encouraging beneficial effects. A major obstacle, howev er, is overcoming vanadium toxicity. Recently, several organically chelated vanadium compounds were found more potent and less toxic than vanadium sal ts in vivo. Such a newly discovered organic chelator of vanadium is describ ed in this review. (C) 2000 Elsevier Science Inc. All rights reserved.