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[Therapeutic potential of vanadium in treating diabetes mellitus]
1Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto, Japan.
Abstract:
The patients suffered from diabetes mellitus (DM) are increasing year by year through the world. DM is classified into two groups, insulin-dependent type 1 and non-insulin-dependent type 2. Recent research has demonstrated that vanadate (VO3-, oxidation state+5) and vanadyl (VO2+, oxidation state+4) both mimic various actions of insulin in cellular systems. In 1985, vanadate given orally as a drinking water to streptozotocin-induced hyperglycemic type 1 diabetic rats (STZ-rats) was found to reduce the high levels of blood glucose down to normal levels and ameliorated many of the aberrations induced by hyperglycemia. In 1990, we proposed first orally active vanadyl complexes such as vanadyl-cysteine methylester and vanadyl-oxalate complexes in STZ-rats. Since then, we have developed orally active vanadyl complexes with different coordination modes. Among them, vanadyl-picolinate complexes with VO(N2O2) coordination mode were found to be potent orally active insulin-mimetic agents, on the basis of the results on in vitro test using isolated rat adipocytes with respect to the inhibition of the release of free fatty acids (FFA) from the cells and in vivo evaluation (intraperitoneal injection and oral administration) in STZ-rats. Based on the results, the usefulness of vanadium complexes in treating and preventing DM has been revealed, proposing a possible action mechanism.
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