Structure-activity relationship of insulin-mimetic vanadyl complexes with VO(N2O2) coordination mode
1998
Sakurai, H. | Fujii, K. | Fujimoto, S. | Fujisawa, Y. | Takechi, K. | Yasui, H.
Insulin-dependent diabetes mellitus (IDDM), characterized by hyperglycemia due to an absolute deficiency of insulin, has been demonstrated to be improved by administration of vanadium complexes in place of insulin injections. Recently, we have found that vanadyl ion as well as vanadyl complexes are relevant to both onset and treatment of IDDM. Therefore, we synthesized vanadyl complexes with different coordination modes such as VO(O4), VO(N4), VO(S4), VO(N2O2), VO(S2O2) and VO(S2O2) and evaluated their insulin-mimetic activities in vitro and in vivo. From the recent investigations on the relationship between structure and insulin-mimetic activity for vanadyl complexes of nitrogenous ligands, vanadyl-picolinate and vanadyl-methylpicolonate complexes with moderate partition coefficient and inhibitory effect of free fatty acid-release from rat adipocytes have been proposed to be long-acting insulin-replacements when they are given orally to streptozotocin-induced IDDM rats. The vanadium distribution and metallokinetic analysis in rats administered the vanadyl complexes were also examined to discuss the action of the complexes.
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