title: Morphological analysis of the pancreas and liver in diabetic KK-A(y) mice treated with zinc and oxovanadium complexes.
abstract: The relationship between biometals, such as zinc (Zn(2+)), vanadium, copper, cobalt, and magnesium ions, and diabetes therapy has been recognized for several years. In particular, the antidiabetic activities of Zn(2+) and oxovanadium (VO(2+)) complexes have been measured using biochemical approaches. In the present study, diabetic KK-A(y) mice were treated with bis(1-oxy-2-pyridine-thiolato)Zn(2+) (Zn(opt)2) and bis(1-oxy-2-pyridine-thiolato)VO(2+) (VO(opt)2) for 4 weeks, and the antidiabetic activities of these metal complexes were evaluated using biochemical and morphological methods. Additionally, zinc gluconate (Zn(glc)2) and bis(ethylmaltolato)VO(2+) (VO(emal)2) were used as reference compounds. Pancreatic islet cells were smaller, and there was a tendency towards a lower islet cell area ratio in Zn(opt)2-treated mice compared with nontreated KK-A(y) mice. Furthermore, plasma insulin concentrations were significantly reduced to 27.2% of insulin concentrations in nontreated KK-A(y) mice. These results suggest that Zn(opt)2 administration provides morphological and biochemical improvements in hyperinsulinaemia. In contrast, in mice that received Zn(glc)2 and VO(2+) complexes, the islet cell size and islet cell area ratio did not differ from those in nontreated controls. Zn(opt)2- and VO(opt)2-treated mice exhibited significantly lower fat deposition and fat deposition area ratio in the liver (63.6% and 65.8% of nontreated KK-A(y) mice, respectively) compared to those observed in nontreated KK-A(y) mice. The differences in morphological improvements of the pancreas and liver owing to Zn(opt)2 or VO(opt)2 treatment may be explained by differences in the sites of actions of Zn(2+) and VO(2+) complexes in different organs in KK-A(y) mice. In conclusion, Zn(opt)2 exhibited superior antidiabetic effects over those of VO(opt)2, and this was owing to greater amelioration of the morphological parameters of the liver and pancreas.
authors.affiliation: Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan. yasui@mb.kyoto-phu.ac.jp.
authors.forename: Takayasu
authors.initials: T
authors.lastname: Moroki
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yoshikawa
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshizawa
authors.forename: Airo
authors.initials: A
authors.lastname: Tsubura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yasui
mesh_terms: D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D056831:Coordination Complexes / Q000494:pharmacology / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000187:drug effects / Q000473:pathology*; D013737:Testis / Q000187:drug effects / Q000473:pathology; D014638:Vanadates / Q000494:pharmacology / Q000627:therapeutic use*; D015032:Zinc / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D056831:Coordination Complexes; D014638:Vanadates; D015032:Zinc