Development of new zinc dithiosemicarbazone complex for use as oral antidiabetic agent

Saori Kadowaki, Masayuki Munekane, Yoji Kitamura, Makoto Hiromura, Shinichiro Kamino, Yutaka Yoshikawa, Hideo Saji, Shuichi Enomoto

研究成果査読

19 被引用数 (Scopus)

抄録

The increasing prevalence of diabetes mellitus (DM) worldwide has underscored the urgency of developing an efficient therapeutic agent. Recently, Zn complexes have been attracting attention due to their antidiabetic activity. In this study, we designed and synthesized a new Zn complex, Zn-3,4-heptanedione-bis(N 4-methylthiosemicarbazonato) (Zn-HTSM), characterized its physicochemical properties, and examined its antidiabetic activity in KK-Ay type 2 DM model mice. It was demonstrated that Zn-HTSM has adequate lipophilicity for the cellular permeability, shows potent hypoglycemic activity, and improves glucose intolerance in KK-Ay mice. We also analyzed the levels of serum adipokines after continuous oral administration of Zn-HTSM. The level of serum leptin of KK-Ay mice is significantly reduced by the treatment of Zn-HTSM. Nevertheless, the levels of serum insulin and adiponectin were not improved. These data suggested that the Zn-HTSM acts on the leptin metabolism. Our present studies indicate that Zn-HTSM is a candidate oral antidiabetic agent for the treatment of type 2 DM.

本文言語English
ページ(範囲)111-119
ページ数9
ジャーナルBiological Trace Element Research
154
1
DOI
出版ステータスPublished - 7月 2013

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 生化学
  • 臨床生化学
  • 無機化学
  • 生化学、医学

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