Antidiabetic copper(II)-picolinate: Impact of the first transition metal in the metallopicolinate complexes
- 作者：Naoko Yasumatsu ; Yutaka Yoshikawa ; Yusuke Adachi ; Hiromu Sakurai
- 关键词：Insulinomimetic activity ; Hypoglycemic effect ; Copper(II)-picolinate complex ; Type 1 diabetes mellitus
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 July 2007
- 卷：15
- 期：14
- 页码：4917-4922
- 文件大小：158 K
摘要
In order to examine the effect of metallopicolinate complexes with first transition metals and develop complexes that are more active than an insulinomimetic leading compound such as oxovanadium(IV)-picolinate complex, VO(pa)2, 10 metallopicolinate complexes were prepared, and their in vitro insulinomimetic and in vivo antidiabetic activities were evaluated. The in vitro activity was estimated by determining the inhibitory effects of these complexes on free fatty acid release from isolated rat adipocytes treated with epinephrine. Among the complexes, Cu(pa)2, and Mn(pa)3 exhibited higher activity than their respective metal ions and better activity than VO(pa)2. Since Cu(pa)2 was non-toxic in the cultured rat hepatic M cells, this complex was given streptozotocin (STZ)-induced type 1-like diabetic mice by single intraperitoneal injection, and found that this complex exhibited a higher hypoglycemic effect than the VO(pa)2 complex. Based on these results, we propose that Cu(pa)2 may be a potent alternative antidiabetic agent.