Anti-hyperglycemic Effect of Long-Term Bis(hinokitiolato)zinc Complex ([Zn(hkt)₂]) Ingestion on Insulin Resistance and Pancreatic Islet Cells Protection in Type 2 Diabetic KK-A[y] Mice

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  • Naito Yuki
    Department of Analytical & Bioinorganic Chemistry, Division of Analytical & Physical Sciences, Kyoto Pharmaceutical University
  • Yoshikawa Yutaka
    Department of Analytical & Bioinorganic Chemistry, Division of Analytical & Physical Sciences, Kyoto Pharmaceutical University Department of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women’s University
  • Shintani Michiko
    Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences Department of Medical Technology, Faculty of Health Sciences, Kobe Tokiwa University
  • Kamoshida Shingo
    Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences
  • Kajiwara Naemi
    Department of Health, Sports, and Nutrition, Faculty of Health and Welfare, Kobe Women’s University
  • Yasui Hiroyuki
    Department of Analytical & Bioinorganic Chemistry, Division of Analytical & Physical Sciences, Kyoto Pharmaceutical University

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  • Anti-hyperglycemic Effect of Long-Term Bis(hinokitiolato)zinc Complex ([Zn(hkt)<sub>2</sub>]) Ingestion on Insulin Resistance and Pancreatic Islet Cells Protection in Type 2 Diabetic KK-A<sup>y</sup> Mice

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<p>Zinc (Zn) is a trace element with anti-diabetes mellitus (anti-DM) effects. Zn complexes exhibit stronger insulin-like activity than Zn ions. Bis(hinokitiolato)zinc complex ([Zn(hkt)2]) was recently reported to be a potent anti-DM candidate. We examined the effects of [Zn(hkt)2] on insulin resistance and pancreatic islet cells through in vivo long-term ingestion studies. In an in vivo study, we performed 4-month long-term [Zn(hkt)2] administration experiments in KK-Ay mice as a type 2 DM animal model. Ingestion of [Zn(hkt)2] resulted in lower blood glucose levels compared with the non-treated KK-Ay mice (control group). Additionally, [Zn(hkt)2] treatment decreased plasma insulin concentration compared with that of the non-treated KK-Ay group. [Zn(hkt)2] treatment resulted in a significant suppression of islet cell enlargement and a significantly decreased number of insulin-positive cells compared with the non-treated KK-Ay control group. The [Zn(hkt)2] treatment group showed the increasing tendency in the amount of Zn levels in peripheral organs; liver, muscle, adipose, and pancreas, compared with the non-treated KK-Ay control group. However, the Zn level in the pancreas of the [Zn(hkt)2] treatment group did not show the significant increase compared with the non-treated KK-Ay control group. This accumulation of Zn in pancreas suggested that [Zn(hkt)2] mainly effects on the peripheral tissue, and [Zn(hkt)2] has the less effect on the pancreas directly. Thus, we concluded that [Zn(hkt)2] exerted the main effect on peripheral organs by ameliorating insulin resistance.</p>

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