Abstract
The effects of several vanadates (ie, orthovanadate, pervanadate, and two stable peroxovanadium compounds) on basal and insulin-stimulated 2-DG transport in insulin target and nontarget cell lines are reported, herein. In nontarget cells, exposure to vanadates (5 × 10−6 to 10−4 mol/L) resulted in 2-DG transport stimulatory responses similar to those observed in 2-DG transport post exposure to 667 nmol/L insulin alone, or insulin in combination with vanadates. In 3T3-L1 adipocytes and L6 myotubes, exposure to a vanadate compound or 67 nmol/L insulin, stimulated 2-DG transport dramatically. Again, this effect on stimulated transport was similar to 2-DG transport post-treatment with the effective vanadates in combination with insulin. While pervanadate or stable peroxovanadates stimulated 2-DG transport at 10−5 to 10−6 mol/L, orthovanadate up to 10−4 mol/L was not effective in stimulating 2-DG transport in any of the cell lines tested. The data indicate that the various peroxovanadates are clearly superior insulin mimetics while a more limited insulin mimesis is observed with orthovanadate over a wide variety of cell types.
Highlights
Vanadium is an essential trace element for higher animals [1, 2], whose specific physiological role has not been elucidated
Effect of various vanadates on 2-DG transport in human fibroblasts In Figure 1a, short term exposure of human fibroblasts (HF) to increasing concentrations of sodium orthovanadate resulted in increased 2-DG transport that appeared to peak at 10−5 mol/L
The stimulation in 2DG transport seen at 10−6 mol/L pVI was not observed with any other vanadate compound in HF
Summary
Vanadium is an essential trace element for higher animals [1, 2], whose specific physiological role has not been elucidated. Studies employing vanadate demonstrated the insulin-like effects which translated into amelioration of blood glucose levels in streptozotocin-treated diabetic rats [7, 14, 15]. This has led to a dramatic increase in studies on vanadium salts as potential treatments for diabetes. Developments using H2O2 plus vanadate resulted in insulin mimetics of short term stability [16]. These compounds were considerably more active than vanadate. This was followed by the synthesis of stable peroxovanadium compounds which were potent phosphotyrosine phosphatase inhibitors and powerful insulin mimetics [17]
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