A novel bis(6-ethylpicolinato)(H(2)O)oxovanadium(IV) complex (
VO(6epa)(2) x (H(2)O)) 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) A, and Z=2). Because
VO(6epa)(2) x (H(2)O) 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)(2) x (H(2)O) was found to normalize the high
blood glucose levels of KK-A(y) mice when given intraperitoneally at doses of 49 micromol/kg
body weight for the first 4 days and then 39 micromol/kg
body weight for 10 days. In addition,
VO(6epa)(2) x (H(2)O) 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) x (H(2)O) 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.