Synthesis of vanadium(IV,V) hydroxamic acid complexes and in vivo assessment of their insulin-like activity.
We synthesized vanadyl (oxidation state +IV) and vanadate (oxidation state +V) complexes with the same hydroxamic acid derivative ligand, and assessed their glucose-lowering activities in relation to the vanadium biodistribution behavior in streptozotocin-induced diabetic mice. When the mice received an intraperitoneal injection of the complexes, the vanadate complex more effectively lowered the elevated glucose levels compared with the vanadyl one. The glucose-lowering effect of the vanadate complex was linearly related to its dose within the range from 2.5 to 7.5 mg V/kg. In addition, pretreatment of the vanadate complex induced a larger insulin-enhancing effect than the vanadyl complex. Both complexes were more effective than the corresponding inorganic vanadium compounds. The vanadyl and vanadate complexes, but not the inorganic vanadium compounds, resulted in almost the same organ vanadium distribution. Consequently, the observed differences in the insulin-like activity between the complexes would reflect the potency of the two compounds in the +IV and +V oxidation states in the subcellular region.
Haratake
Mamoru
M
Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, 852-8521, Japan. haratake@net.nagasaki-u.ac.jp
Fukunaga
Masashi
M
Ono
Masahiro
M
Nakayama
Morio
M
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018360:Crystallography, X-Ray; D003920:Diabetes Mellitus / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D004578:Electron Spin Resonance Spectroscopy; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008968:Molecular Conformation; D013311:Streptozocin / Q000494:pharmacology; D017968:Vanadium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
D001786:Blood Glucose; D006877:Hydroxamic Acids; D007328:Insulin; D017968:Vanadium Compounds; D013311:Streptozocin