title: Development of a novel antidiabetic zinc complex with an organoselenium ligand at the lowest dosage in KK-A(y) mice.
abstract: Diabetes mellitus (DM) is a considerably diagnosed metabolic disease and a serious problem worldwide. We prepared various zinc complexes and studied their potential for use as new antidiabetic agents. In this study, we synthesized a seleniferous zinc complex, di(2-selenopyridine-N-oxidato)zinc(II) ([ZPS]) that has a Zn(Se2O2) coordination mode. Analyses of structure-activity relationships between its insulin-like activity and the coordination mode of [ZPS]-related complexes showed that it had high insulin-like activity. Hypoglycemic effects of [ZPS] on type 2 diabetic KK-A(y) mice were exerted at the lowest dose administered (1.25-2.5 mg Zn/kg body weight), unlike previously synthesized zinc complexes. Furthermore, [ZPS] afforded us a new advantage; we were able to investigate the tissue distribution of the ligand by measuring the amount of selenium in the organs of [ZPS]-treated mice. Gastrointestinal absorption and tissue penetration of zinc derived from [ZPS] in ddY mice, which was monitored using an isotope tracer technique, was significantly increased compared to that of ZnCl2. These results suggest that [ZPS] has superior antidiabetic effects compared to previously reported zinc complexes, and is thus a potential novel antidiabetic agent that facilitates the possibility of organoselenium ligands as new metal delivery systems for treating DM.
authors: Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Chemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Kyoto 607-8414, Japan. sfujimoto.d12@lif.kyoto-u.ac.jp
authors: Shigeyuki
authors: S
authors: Fujimoto
authors: Hiroyuki
authors: H
authors: Yasui
authors: Yutaka
authors: Y
authors: Yoshikawa
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006207:Half-Life; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008024:Ligands; D008297:Male; D051379:Mice; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D015032:Zinc / Q000737:chemistry*
chemical_list: D001786:Blood Glucose; D056831:Coordination Complexes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008024:Ligands; D016566:Organoselenium Compounds; D015032:Zinc; C582988:di(2-selenopyridine-N-oxidato)zinc(II)