title: Bis(6-ethylpicolinato)oxovanadium(IV) complex with normoglycemic activity in KK-A(y) mice.
abstract: 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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sasagawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawabe
authors.forename: Hiromu
authors.initials: H
authors.lastname: Sakurai
authors.forename: Yoshitane
authors.initials: Y
authors.lastname: Kojima
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010848:Picolinic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D014638:Vanadates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D009942:Organometallic Compounds; D010848:Picolinic Acids; C447645:bis(6-ethylpicolinato)oxovanadium(IV); C095866:bis(picolinato)oxovanadium(IV); D014638:Vanadates