Morphological analysis of the pancreas and liver in diabetic KK-A(y) mice treated with zinc and oxovanadium complexes

作者：Moroki Takayasu; Yoshikawa Yutaka; Yoshizawa Katsuhiko; Tsubura Airo; Yasui Hiroyuki^*

来源：Metallomics, 2014, 6(9): 1632-1638.

DOI：10.1039/c4mt00087k

The relationship between biometals, such as zinc (Zn2+), vanadium, copper, cobalt, and magnesium ions, and diabetes therapy has been recognized for several years. In particular, the antidiabetic activities of Zn2+ and oxovanadium (VO2+) 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)Zn2+ (Zn(opt)(2)) and bis(1-oxy-2-pyridine- thiolato)VO2+ (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)VO2+ (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 VO2+ 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 Zn2+ and VO2+ 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.

• 出版日期2014