Oral Administration of Bis(aspirinato)zinc(II) Complex Ameliorates Hyperglycemia and Metabolic Syndrome-Like Disorders in Spontaneously Diabetic KK-Ay Mice: Structure–Activity Relationship on Zinc–Salicylate Complexes
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概要
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In recent years, the number of patients suffering from diseases, such as cancer, apoplexy, osteoporosis, hypertension, and type 2 diabetes mellitus is increasing worldwide. Type 2 diabetes, a lifestyle-related disease, is recognized as a serious disease. Various types of pharmaceutics for diabetes have been used. Since the relationship between diabetes and biometals such as vanadium, copper, and zinc ions has been recognized for many years, we have been developing the anti-diabetic metal complexes as new candidates. We found that several zinc(II) (Zn) complexes exhibit glucose-lowering activity for treating type 2 diabetes. High doses of salicylates have been known to reverse hyperglycemia and hyperinsulinemia in type 2 diabetic patients. These findings strongly suggest that the combined use of Zn and salicylates achieves the synergism in treating type 2 diabetes. Because aspirin, acetyl salicylic acid, has a chelating ability, we used it as a ligand to Zn. Several Zn–salicylate complexes were prepared and their biological activities were examined in this study. The complexes with an electron-withdrawing group in the ligand exhibited higher in vitro insulinomimetic activity than those of Zn complexes with an electron-donating group in the ligand. When bis(aspirinato)Zn (Zn(asp)2) complex was orally administered on KK-Ay mice with hereditary type 2 diabetes, the diabetic state was improved. In addition, this complex exhibited normalizing effects on serum adiponectin level and high blood pressure in metabolic syndrome. In conclusion, Zn(asp)2 complex is newly proposed as a potent anti-diabetic and anti-metabolic syndrome agent.
- 公益社団法人 日本薬学会の論文
著者
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Yasui Hiroyuki
京都薬科大学 代謝分析学教室
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Yasui Hiroyuki
Department Of Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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YOSHIKAWA Yutaka
Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University
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Sakurai Hiromu
Department Of Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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Hattori Masakazu
Division Of Diabetes Clinical Research Center National Hospital Organization Kyoto Medical Center
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Adachi Yusuke
Department Of Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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Yoshikawa Yutaka
Department Of Analytical And Bioinorganic Chemistry Kyoto Pharmaceutical University
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Hattori Masakazu
Division of Diabetes, Clinical Research Institute for Endocrine and Metabolic Diseases, National Hospital Organization, Kyoto Medical Center
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Sakurai Hiromu
Department of Pharmaco-analytical and Biocoordination Chemistry, Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science
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