Oral administration of a zinc complex improves type 2 diabetes and metabolic syndromes

Yusuke Adachi, Jiro Yoshida, Yukihiro Kodera, T. Kiss, T. Jakusch, E. Enyedy, Yutaka Yoshikawa, Hiromu Sakurai

Research output: Contribution to journalArticle

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Abstract

Previously, we reported that intraperitoneal injections of the Zn(II) complex (Zn(alx)2) with allixin, which is isolated from dry garlic, with a Zn(O4) coordination environment, exhibited high anti-diabetic effects in obesity-linked type 2 diabetic KKAy mice. However, this complex exhibited low activity when administered orally. To improve the effect of Zn(alx)2, we prepared a novel Zn(II) complex with the allixin-derivative bis(1,6-dimethyl-3-hydroxy-5-methoxy-2-pentyl-1,4-dihydropyridine-4- thionato)Zn(II), abbreviated as Zn(II)-thioallixin-N-methyl (Zn(tanm)2), having a Zn(S2O2) coordination environment; this complex has extremely high in vitro insulin-like activity. Because Zn was extensively absorbed from the gastrointestinal tract when Zn(tanm)2 was orally administered, its anti-diabetic effects were examined in KKAy mice. Daily oral administrations of Zn(tanm)2 for 4 weeks in KKAy mice significantly improved hyperglycemia, glucose intolerance, insulin resistance, hyperleptinemia, obesity, and hypertension. Interestingly, Zn(tanm)2 increased depressed plasma adiponectin levels in the mice. Here, we propose that Zn(tanm)2 will be an orally active therapeutic for obesity-linked type 2 diabetes and metabolic syndromes.

Original languageEnglish
Pages (from-to)165-170
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume351
Issue number1
DOIs
Publication statusPublished - Dec 8 2006

Fingerprint

Medical problems
Type 2 Diabetes Mellitus
Oral Administration
Zinc
Insulin
Obesity
Adiponectin
Derivatives
Plasmas
Glucose
Garlic
Glucose Intolerance
Intraperitoneal Injections
Hyperglycemia
Insulin Resistance
Gastrointestinal Tract
Hypertension
allixin
1,4-dihydropyridine
Therapeutics

Keywords

  • Adiponectin
  • Hypertension
  • Insulin resistance
  • Leptin resistance
  • Metabolic syndromes
  • Obesity-linked type 2 diabetes
  • Zn(II) complex

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Oral administration of a zinc complex improves type 2 diabetes and metabolic syndromes. / Adachi, Yusuke; Yoshida, Jiro; Kodera, Yukihiro; Kiss, T.; Jakusch, T.; Enyedy, E.; Yoshikawa, Yutaka; Sakurai, Hiromu.

In: Biochemical and Biophysical Research Communications, Vol. 351, No. 1, 08.12.2006, p. 165-170.

Research output: Contribution to journalArticle

Adachi, Yusuke ; Yoshida, Jiro ; Kodera, Yukihiro ; Kiss, T. ; Jakusch, T. ; Enyedy, E. ; Yoshikawa, Yutaka ; Sakurai, Hiromu. / Oral administration of a zinc complex improves type 2 diabetes and metabolic syndromes. In: Biochemical and Biophysical Research Communications. 2006 ; Vol. 351, No. 1. pp. 165-170.
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