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

Adachi, Yusuke; Yoshida, Jiro; Kodera, Yoshihisa; Kiss, Tamás; Jakusch, Tamás; Enyedy, Éva A.; Yoshikawa, Yutaka; Sakurai, Hiromu

doi:10.1016/j.bbrc.2006.10.014

Cited by 79 publications

(75 citation statements)

References 27 publications

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“…Type 2 diabetes risk is associated with a polymorphism of the pancreatic β-cell-specific zinc transporter ZnT-8 (SLC30A8), which provides zinc for insulin maturation and/or storage in these cells (26,27). Antidiabetogenic and insulinomimetic properties of zinc are supported by the results from zinc supplementation in animals and humans (28,29) and are now explored therapeutically by synthesizing and testing zinc-containing drugs (30). Because cardiovascular disease is the leading cause of mortality in type 2 diabetes, there is a major research focus on the diabetic heart.…”

Section: Implications For Diseases With Particular Emphasis On Diabetesmentioning

confidence: 99%

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Maret

Krężel

2007

Mol Med

171

132

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Zinc is involved in virtually all aspects of cellular and molecular biology as a catalytic, structural, and regulatory cofactor in over 1000 proteins. Zinc binding to proteins requires an adequate supply of zinc and intact molecular mechanisms for redistributing zinc ions to make them available at the right time and location. Several dozen gene products participate in this process, in which interactions between zinc and sulfur donors determine the mobility of zinc and establish coupling between cellular redox state and zinc availability. Specifically, the redox properties of metallothionein and its apoprotein thionein are critical for buffering zinc ions and for controlling fluctuations in the range of picomolar concentrations of "free" zinc ions in cellular signaling. Metallothionein and other proteins with sulfur coordination environments are sensitive to redox perturbations and can render cells susceptible to injury when oxidative stress compromises the cellular redox and zinc buffering capacity in chronic diseases. The implications of these fundamental principles for zinc metabolism in type 2 diabetes are briefly discussed.

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Section: Implications For Diseases With Particular Emphasis On Diabetesmentioning

confidence: 99%

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Maret

Krężel

2007

Mol Med

171

132

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“…Previous reports showed that the effective dose of Zn complexes for anti-DM activity is approximately 15 mg Zn/kg BW. Furthermore, we prepared an HFD in vivo 31: 1145-1151 (2017) 1146 (26,27).…”

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confidence: 99%

Beneficial Effect of Bis(Hinokitiolato)Zn Complex on High-fat Diet-induced Lipid Accumulation in Mouse Liver and Kidney

Naito

Yoshikawa

Yoshizawa

et al. 2017

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Abstract. Background/Aim: Metabolic syndrome-induced lifestyle-related diseases include diabetes mellitus (DM) and hypertension, and Zn-based compounds have effects on DM. We aimed to investigate the ameliorating effects of bis(hinokitiolato) Zn, [Zn(hkt) 2 The westernization of eating habits has increased the intake of fat. Metabolic syndrome, which is caused by these changing dietary habits, induces diabetes mellitus (DM) or hypertension (1, 2). There are numerous reports on the effects of a high-fat diet (HFD) intake on health, and the most serious and important are dyslipidaemia, which is characterised by hypertriglyceridaemia, hypercholesterolaemia, and fatty liver (3, 4).Numerous researchers have reported the effects of many organic or inorganic compounds on various organs, leading to disorders such as fatty liver or diabetic nephropathy (5, 6). Furthermore, other studies have reported that some compounds, even known as beneficial food materials, can worsen a disease condition (7,8). These reports suggest that careful considerations are required to understand the correct use of these food materials and evaluate their effects on both biochemical parameters and organ morphology. In particular, dyslipidaemia, which is a risk factor for cardiovascular disease, should be prevented.Pioglitazone is known to exhibit efficacy in the treatment of DM owing to its blood glucose lowering, glycated haemoglobin (HbA1c) improvement, and glucose tolerance ameliorating effects (9, 10). Furthermore, numerous researchers have reported the anti-DM effect of Zn in in vivo experiments (11-13). For example, Zn compound 1) increased Akt-phosphorylation, as well as inhibited tyrosine-protein phosphatase non-receptor type 1B (PTP1B) and phosphatase and tensin homolog (PTEN) in 3T3-L1 adipocytes; and 2) inhibited alpha-glucosidase and 3) activated phosphodiesterase (14-18). Furthermore, only a few studies such as that of Moroki et al. (19) have reported experiments showing the effects of Zn complexes on lipid metabolism. Thus, the effects of Zn compounds on lipid metabolism have not been sufficiently examined yet.The experimental animals were fed an HFD or highfructose diet to establish the metabolic syndrome or DM model (20,21). Therefore, this study examined the histopathology of the livers and kidneys of C57BL/6J mice 1145

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“…In recent years, zinc preparations, particularly polaprezinc, have been used as an antiˆbrotic agent in patients with chronic hepatitis type C. 11) Insulinomimetic eŠects of zinc(II) complexes Zinc not only contributes to the synthesis and action of insulin 1,4) but also generates insulin-like eŠects in an insulin-independent manner. 6,12) The group of Sakurai et al has synthesized Zn(II) complexes exhibiting hypoglycemic eŠects (Fig. 4).…”

Section: Physiologic Functions Of Zincmentioning

confidence: 99%

“…1,4) Particularly, some orally active Zn(II) complexes have dramatically ameliorated the pathophysiology of diabetes mellitus and metabolic syndrome in animal experiments. 6) This paper reviews the physiologic functions of zinc and recent trends in zinc therapy for a better understanding of the clinical features of zinc deˆciency and zinc therapy.…”

Section: Introductionmentioning

confidence: 99%

Zinc Deficiency and Clinical Practice -Validity of Zinc Preparations-

Yanagisawa

2008

YAKUGAKU ZASSHI

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Zinc is an essential trace element and serves as the active center of approximately 300 enzymes. Therefore, zinc deˆciency may be associated with a variety of clinical features such as hypogeusia, hyposmia, growth retardation, dermatitis, alopecia, gonadal hypofunction, abnormal pregnancy, susceptibility to infections, delayed wound healing, impaired glucose tolerance, and increased carcinogenesis. Zinc deˆciency was reported to be on the increase in the Nagano Study conducted from 2003 to 2005. Zinc therapy is classiˆed into two categories, zinc-supplementary and -speciˆc treatments. Ordinarily, zinc-supplementary therapy is carried out for the symptoms and diseases caused by zinc deˆciency. On the other hand, zinc-speciˆc therapy is applied to obtain copper-and iron-chelating, antiˆbrotic, and antidiabetic eŠects. The availability of zinc-speciˆc therapy is now conˆrmed in humans and animals. Hereafter, the safety of zinc therapy needs to be examined further.

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

Cited by 79 publications

References 27 publications

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Cellular Zinc and Redox Buffering Capacity of Metallothionein/Thionein in Health and Disease

Beneficial Effect of Bis(Hinokitiolato)Zn Complex on High-fat Diet-induced Lipid Accumulation in Mouse Liver and Kidney

Zinc Deficiency and Clinical Practice -Validity of Zinc Preparations-

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