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

• Published in: Biological trace element research Vol. 192; no. 2; pp. 206 - 213
• Main Authors: Naito, Yuki, Yamamoto, Hiroaki, Yoshikawa, Yutaka, Yasui, Hiroyuki
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-12-2019; Springer Nature B.V
• Subjects: Adipose tissue; Adipose Tissue - drug effects; Adipose Tissue - metabolism; AKT protein; Anaesthesia; Anesthesia; Animal tissues; Animals; Bioavailability; Biochemistry; Biomedical and Life Sciences; Biotechnology; Body organs; Diabetes; Diabetes mellitus; Distribution; Dose-Response Relationship, Drug; Glucose; Glycogen; In vivo methods and tests; Inductively coupled plasma mass spectrometry; Injection; Insulin; Isoflurane; Life Sciences; Liver; Male; Mass spectrometry; Mass spectroscopy; Mice; Mice, Inbred ICR; Molecular modelling; Molecular Structure; Muscles; Musculoskeletal system; Nutrition; Oncology; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Organs; Phosphorylation; Phosphorylation - drug effects; Proto-Oncogene Proteins c-akt - metabolism; Signal transduction; Signaling; Skeletal muscle; Structure-Activity Relationship; Tissue; Tissue Distribution; Weight; Wet weight; Zinc; Zinc - analysis; Zinc compounds; Insulin-like effect; Akt phosphorylation; Zinc complex; Zn(mal); Diabetes; ]; Zinc; Zn(mal)2
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-019-1648-3

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.