Investigating the target organs of novel anti-diabetic zinc complexes with organo‑selenium ligands

Abstract

Diabetes mellitus (DM) is a serious problem worldwide and is becoming increasingly prevalent. Previously, we reported the use of various zinc (Zn) complexes as new anti-diabetic agents. In this study, we synthesized novel organo‑selenium (Se) Zn complexes with hydroxy-pyrone derivatives that have a Zn(Se2O2) coordination mode. The results of in vitro insulin-mimetic analyses showed that the compound bis(3-hydroxy-2-methyl-4(H)-pyran-4-seleno)Zn ([Zn(hmps)2]) exhibited the strongest activity among all the complexes. In the in vivo studies of Zn complexes with 3-hydroxy-2-methyl-4(H)-pyran-4-one, maltol, (hmpo) derivatives, [Zn(hmps)2] exhibited a stronger anti-diabetic effect than bis(3-hydroxy-2-methyl-4(H)-pyran-4-one)Zn ([Zn(hmpo)2]), which had a Zn(O4) coordination mode. Additionally, we investigated the organ distribution of both Zn and Se by determining the amounts of these elements in the organs of [Zn(hmps)2]-administered mice. We then evaluated the effect of treatment with Zn complexes on hepatic lipid accumulation and pancreatic islet hypertrophy by hematoxylin and eosin (HE) histological staining. Zn complexes were found to improve the hypertrophy in the pancreas. There were some reports that Se-containing Zn complexes such as di(2-selenopyridine-N-oxidato)Zn(II) ([ZPS]) were effective for treating diabetes mellitus, so in this study, we examined different types of zinc complexes with organo‑selenium ligands.