In Vivo Effect of Bis(Maltolato)Zinc(II) Complex on Akt Phosphorylation in Adipose Tissues of Mice

  • Yuki NaitoEmail author
  • Hiroaki Yamamoto
  • Yutaka Yoshikawa
  • Hiroyuki Yasui


The risk of serious complication gradually increases as diabetes mellitus (DM) progresses. Thus, strategies for the prevention and delay of symptom progression are urgently needed. Previously, we synthesized zinc (Zn) complexes estimated to have a high bioavailability and evaluated their insulin-like anti-DM effects. However, in vivo studies of the effects of Zn compounds on the insulin signaling pathway and the molecular mechanisms underlying the anti-diabetic activities of Zn complexes were unresolved. In this study, we evaluated the effect of bis(maltolato)zinc(II) complex [Zn(mal)2] on male ICR mice (6-week-old) that received intraperitoneal (i.p.) injection of [Zn(mal)2]. The liver, skeletal muscle, and adipose tissues were collected from mice under anesthesia with isoflurane 40 or 90 min after i.p. injection. The [Zn(mal)2]-treatment did not affect Akt phosphorylation in the liver or skeletal muscle. In contrast, in adipose tissues, [Zn(mal)2]-treatment showed increased Akt phosphorylation at 40 min and 90 min after injection (p < 0.01 vs. control). The Zn distribution in the organs was evaluated using inductively coupled plasma mass spectrometry. Notably, high Zn accumulation was observed in the adipose tissue (4.5 ± 2.7 μg Zn/g wet weight), and this value was about six times higher than in the control mice (p < 0.01). Based on the observed organ-specific distribution of [Zn(mal)2], we suggest that it does not directly promote glycogen synthesis in the liver but may impact the insulin signaling pathway in adipose tissues. Our results may contribute to the clinical use of zinc compounds for the treatment of diabetes.


Diabetes Zinc Zinc complex [Zn(mal)2Insulin-like effect Akt phosphorylation 



The authors would like to thank the members of the Analytical Center of KPU for the elemental analysis and mass spectra measurements. We would like to thank Editage ( for English language editing.

Funding Information

This work was supported by JSPS KAKENHI grant number JP17K18231.

Compliance with Ethical Standards

Conflicts of Interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Department of Analytical & Bioinorganic Chemistry, Division of Analytical & Physical SciencesKyoto Pharmaceutical UniversityKyotoJapan
  2. 2.Department of Health, Sports, and Nutrition, Faculty of Health and WelfareKobe Women’s UniversityKobeJapan

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