Bis(6-ethylpicolinato)oxovanadium(IV) complex with normoglycemic activity in KK-A(y) mice

A novel bis(6-ethylpicolinato)(H2O)oxovanadium(IV) complex (VO(6epa)(2)(.)(H2O)) was prepared and its structure was revealed by X-ray analysis (space group Pc(#7), a=10.838(2), b=11.148(5), c=16.642(3) Angstrom, and Z=2). Because VO(6epa)(2)-(H2O) exhibited higher in vitro insulinomimetic activity compared to that of vanadyl sulfate in terms of inhibition of free fatty acid (FFA) release from isolated rat adipocytes in the presence of epinephrine, its in vivo effect on whether the complex has a blood glucose normalizing effect was examined in KK-A(y) mice, a model animal of type 2 diabetes mellitus. VO(6epa) (H2O) was found to normalize the high blood glucose levels of KK-A(y) mice when given intraperitoneally at doses of 49 mumol/kg body weight for the first 4 days and then 39 mumol/kg body weight for 10 days. In addition, VO(6epa)(2)(.)(H2O) improved glucose tolerance ability as examined by the oral glucose test and seemed to have little toxicity in terms of serum parameters. VO(6epa)(2)(.)(H2O) showed higher normoglycemic activity than bis(6-methylpicolinato)oxovanadium(IV) (VO(6mpa)(2)) at the same dose. These results indicated that greater enhancement of the blood glucose normalizing effect in KK-A(y) mice by ethyl substitution compared to methyl substitution may be due to its being more strongly lipophilic. (C) 2002 Elsevier Science B.V. All rights reserved.