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.
Highlights
The number of adults with diabetes mellitus (DM) has been increasing annually and is expected to reach 642 million worldwide by 2040 [1]
We have evaluated the anti-diabetic effects of Zn complexes using KKAy mice, few Zn complexes have been evaluated for their anti-diabetic effects using mouse models of type 2 DM arising from different pathogenic mechanisms
Our findings indicated that Zn complexes exert potent anti-diabetic effects in ob/ob mice as well as in KKAy mice, and that these likely occur via a normalizing effect on insulin secretion and fasting blood glucose level
Summary
The number of adults with diabetes mellitus (DM) has been increasing annually and is expected to reach 642 million worldwide by 2040 [1]. To treat DM, diet modification, exercise therapy, and administration of various anti-diabetic agents are utilized. The agents available for clinical use with DM are associated with problems such as physical and mental discomfort owing to daily insulin injections; some of these agents have side effects [3]. The development of new types of anti-diabetic agents is essential to treat DM and to improve the quality of life (QOL) in patients with this disorder. In 1980, Coulston and Dandona reported the first insulin-mimetic activity of Zn ions on rat adipocytes [5]. Several research groups have attempted to confirm the insulin-mimetic activity of Zn ion via analysis of the anti-diabetic effects of Zn ions in mouse models of type 1 and type 2 DM [6,7,8]
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