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

• Published in: Metallomics 2014, Vol.6 (9), p.1632-1638
• Main Authors: Moroki, Takayasu, Yoshikawa, Yutaka, Yoshizawa, Katsuhiko, Tsubura, Airo, Yasui, Hiroyuki
• Format: Article
• Language: English
• ISSN: 1756-5901; 1756-591X
• DOI: 10.1039/C4MT00087K

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.