Insulinomimetic Zinc(II) Complexes with Natural Products: In Vitro Evaluation and Blood Glucose Lowering Effect in KK-Ay Mice with Type 2 Diabetes Mellitus

Kojima, Yoshitane; Yoshikawa, Yutaka; Ueda, Eriko; Ueda, Rie; Yamamoto, Shuhei; Kumekawa, Katsumi; Yanagihara, Naohisa

doi:10.1248/cpb.51.1006

Cited by 23 publications

(20 citation statements)

References 25 publications

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“…It has been suggested that an additional supplement of zinc may be useful in diabetics. Similar protective effects of zinc on blood glucose levels have been emphasized in other studies [6,[25][26][27].…”

Section: Discussionsupporting

confidence: 82%

The Influence of Zinc Supplementation on the Pancreas of Streptozotocin-Diabetic Rats

2009

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The aim of this study was to investigate the effects of zinc supplementation on somatostatin and insulin peptide expressions and biochemical parameters. Six- to 6.5-month-old female Swiss albino rats weighing 150-200 g were used. The animals were divided into four groups: group I: control (intact) animals; group II: control animals given zinc sulfate; group III: streptozotocin (STZ)- induced diabetic animals; group IV: STZ-induced diabetic animals given zinc sulfate. Fasting blood glucose and glutathione levels were measured at 0, 1, 30 and 60 days. On day 60, the pancreas tissue and blood samples were taken from the animals. Zinc supplementation caused a decrease in hyperglycemia, as well as weight increase. Zinc sulfate treatment did not affect the number of somatostatin-immunoreactive cells in the pancreas. More insulin-immunoreactive cells were observed in the pancreatic islets of the diabetic+zinc sulfate group than in the diabetic group, although it was not statistically significant. The results show that zinc supplementation may prevent diabetes in experimental animals.

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Section: Discussionsupporting

confidence: 82%

The Influence of Zinc Supplementation on the Pancreas of Streptozotocin-Diabetic Rats

2009

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“…Daily intraperitoneal injections of these Zn(II) complexes for 14 days attenuated hyperglycemia, hyperinsulinemia and hyperlipidemia, and improved oral glucose tolerance and HbA1c values in KK-A y mice (Type 2 diabetes model) without negative effects on indices of renal and hepatic function (Yoshikawa et al 2001Kojima et al 2003). Similar results have been reported in GK rats (non-obese Type 2 diabetes model) given Zn(II) complexes intraperitoneally or by oral administration for 30-45 days (Fugono et al 2002).…”

Section: Zn and Type 2 Diabetes Modelssupporting

confidence: 72%

Zinc, the Pancreas, and Diabetes: Insights from Rodent Studies and Future Directions

2005

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Molecular and cellular studies have demonstrated several roles for zinc (Zn) in insulin production and the consequent actions of insulin on metabolism. Clinical and epidemiological studies suggest that reduced Zn status is associated with diabetes. Investigations of Zn in rodent models of diabetes have provided a valuable link for understanding the molecular, cellular, clinical and epidemiological observations in the context of inter-organ metabolism and the metabolic disturbances of diabetes. This review highlights some of the current knowledge and future research directions for the role of Zn in the pancreas and diabetes based on rodent studies and experimental manipulations of Zn. Overall, Zn supplementation is effective for preventing or ameliorating diabetes in several rodent models of Type 1 and Type 2 diabetes. Studies with chemically-induced Type 1 diabetes indicate that the protective effects of Zn involve antioxidant mechanisms whether it is Zn alone (as an antioxidant), Zn induction of metallothionein or Zn inhibition of redox-sensitive transcription factors. Further studies are needed to identify the mechanism(s) for Zn protection in Type 2 diabetes, including pancreatic and peripheral effects. Experimental manipulations of Zn status in rodent models of diabetes provide a valuable approach to explore mechanisms for the protective effects of Zn; however, long term clinical studies establishing safety (lack of toxicity) and efficacy are required before any recommendations can be made for people with diabetes.

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“…In addition, Zn salts have several disadvantages such as low absorption and short turnover. Zn complexes with superior properties that will overcome these limitations are being developed (Kojima et al 2003;Song et al 2003;Yoshikawa et al 2004). A promising future for Zn supplementation will warrant further studies.…”

Section: Resultsmentioning

confidence: 99%

Zinc and the Diabetic Heart

Song

Wang

et al. 2005

Biometals

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Zinc (Zn) is an essential mineral that is required for various cellular functions. Its abnormal metabolism is related to certain disorders such as diabetic complications. Oxidative stress has been considered as the major causative factor for diabetic cardiomyopathy. Zn has a critical antioxidant action in protecting the heart from various oxidative stresses. Zn deficiency was found to be a risk factor for cardiac oxidative damage and supplementation with Zn provides a significant prevention of oxidative damage to the heart. Diabetes causes a significant systemic oxidative stress and also often is accompanied by Zn deficiency that increases the susceptibility of the heart to oxidative damage. Therefore, there is a strong rationale to consider the strategy of Zn supplementation to prevent or delay diabetic cardiomyopathy. This short article collects the preliminary evidence, based on our own studies and those by others, for a preventive effect of Zn supplementation on diabetes-induced injury to the heart in animals and under in vitro conditions. Possible mechanisms by which Zn supplementation prevents diabetic heart disease are discussed. They include an antioxidant action of Zn, insulin function and metallothionein induction. In the final section, the future of Zn supplementation for diabetic patients is also briefly discussed. Although Zn supplementation has not been clinically used to prevent diabetic complications, because several issues need to be addressed, the fact that Zn supplementation is being used clinically for other disorders encourages us to explore its direct clinical application for the prevention of diabetic cardiomyopathy.

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Insulinomimetic Zinc(II) Complexes with Natural Products: In Vitro Evaluation and Blood Glucose Lowering Effect in KK-Ay Mice with Type 2 Diabetes Mellitus

Cited by 23 publications

References 25 publications

The Influence of Zinc Supplementation on the Pancreas of Streptozotocin-Diabetic Rats

The Influence of Zinc Supplementation on the Pancreas of Streptozotocin-Diabetic Rats

Zinc, the Pancreas, and Diabetes: Insights from Rodent Studies and Future Directions

Zinc and the Diabetic Heart

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