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Int. J. Mol. Sci. 2017, 18(12), 2647; doi:10.3390/ijms18122647

Anti-Diabetic Effect of Organo-Chalcogen (Sulfur and Selenium) Zinc Complexes with Hydroxy-Pyrone Derivatives on Leptin-Deficient Type 2 Diabetes Model ob/ob Mice

1
Department of Analytical and Bioinorganic Chemistry, Division of Analytical and Physical Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan
2
Department of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women’s University, 4-7-2 Minatojima-nakamachi, Chuo-ku, Kobe 650-0046, Japan
*
Authors to whom correspondence should be addressed.
Received: 13 November 2017 / Revised: 30 November 2017 / Accepted: 2 December 2017 / Published: 7 December 2017
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Abstract

Since the discovery of the anti-diabetic effects of zinc (Zn) complex, we synthesized several Zn complexes and evaluated their effects using the KKAy type 2 diabetes mouse model. Recently, we demonstrated that organo-chalcogen (sulfur and selenium) Zn complexes elicit strong anti-diabetic effects. In this study, we treated leptin-deficient ob/ob mice with organo-chalcogen Zn complexes, and evaluated the resulting anti-diabetic effects in a mouse model of diabetes arising from pathogenic mechanisms different from those in KKAy mice. C57BL/6J ob/ob mice orally received either bis(3-hydroxy-2-methyl-4(H)-pyran-4-thiono)Zn, [Zn(hmpt)2] or bis(3-hydroxy-2-methyl-4(H)-pyran-4-seleno)Zn, [Zn(hmps)2], daily for 28 days. Both Zn complexes elicited potent blood glucose-lowering effects and improved HbA1c values. Moreover, glucose intolerance improved as evidenced by the oral glucose tolerance test, and fasting plasma insulin levels decreased in both types of Zn complex-treated mice. Zn concentrations in the liver and pancreas of [Zn(hmpt)2]-treated mice and in the pancreas of [Zn(hmps)2]-treated mice were increased, respectively. The results suggest that the present Zn complexes mainly exerted an anti-diabetic effect in the liver or pancreas. This study is the first to demonstrate that potent Zn complexes elicit anti-diabetic effects in not only KKAy but also ob/ob mice via a normalizing effect on insulin secretion and fasting blood glucose levels. View Full-Text
Keywords: diabetes mellitus; organo-chalcogen zinc complexes; ob/ob mice; anti-diabetic effect; inductively coupled plasma mass spectrometry; morphological analysis diabetes mellitus; organo-chalcogen zinc complexes; ob/ob mice; anti-diabetic effect; inductively coupled plasma mass spectrometry; morphological analysis
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Nishiguchi, T.; Yoshikawa, Y.; Yasui, H. Anti-Diabetic Effect of Organo-Chalcogen (Sulfur and Selenium) Zinc Complexes with Hydroxy-Pyrone Derivatives on Leptin-Deficient Type 2 Diabetes Model ob/ob Mice. Int. J. Mol. Sci. 2017, 18, 2647.

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