Insulin-like effects of vanadium: basic and clinical implications.
Most mammalian cells contain vanadium at a concentration of about 20 nM, the bulk of which is probably in the reduced vanadyl (+4) form. Although this trace element is essential and should be present in the diet in minute quantities, 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 inhibitor of Na+,K+-ATPase as well as of other related phosphohydrolases. In 1980 vanadium was reported to mimic the metabolic effects of insulin in rat adipocytes. During the last decade, vanadium has been found to act in an insulin-like manner in all three main target tissues of the hormone, namely skeletal muscles, adipose, and liver. Subsequent studies revealed that the action of vanadium salts is mediated through insulin-receptor independent alternative pathway(s). The investigation of the antidiabetic potency of vanadium soon ensued. Vanadium therapy was shown to normalize blood glucose levels in STZ-rats and to cure many hyperglycemia-related deficiencies. Therapeutic effects of vanadium were then demonstrated in type II diabetic rodents, which do not respond to exogenously administered insulin. Finally, clinical studies indicated encouraging beneficial effects. A major obstacle, however, is overcoming vanadium toxicity. Recently, several organically chelated vanadium compounds were found more potent and less toxic than vanadium salts in vivo. Such a newly discovered organic chelator of vanadium is described in this review.
Goldwaser
I
I
Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel.
Gefel
D
D
Gershonov
E
E
Fridkin
M
M
Shechter
Y
Y
D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects; D051381:Rats; D014639:Vanadium / Q000737:chemistry / Q000494:pharmacology*
D007328:Insulin; D014639:Vanadium