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

Abstract

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.