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慢性低浓度镉暴露对大鼠的影响:葡萄糖代谢的性别特异性紊乱。

Impact of chronic and low cadmium exposure of rats: sex specific disruption of glucose metabolism.

机构信息

Univ. Grenoble Alpes, Inserm, Laboratory of Fundamental and Applied Bioenergetics (LBFA), 38000, Grenoble, France.

Univ. Grenoble Alpes, Inserm, Laboratory of Fundamental and Applied Bioenergetics (LBFA), 38000, Grenoble, France; Grenoble University Hospital, Grenoble, France.

出版信息

Chemosphere. 2018 Sep;207:764-773. doi: 10.1016/j.chemosphere.2018.05.099. Epub 2018 May 20.

DOI:10.1016/j.chemosphere.2018.05.099
PMID:29859488
Abstract

BACKGROUND

Several epidemiological and animal studies suggest a positive association between cadmium (Cd) exposure and incidence of type 2 diabetes, but the association remains controversial. Besides, the experimental data have mainly been obtained with relatively high levels of Cd, over various periods of time, and with artificial routes of administration.

OBJECTIVES

Do environmental exposures to Cd induce significant disruption of glucose metabolism?

METHODS

Adults Wistar rats were exposed for three months to 0, 5, 50 or 500 μg.kg.d of CdCl in drinking water. Relevant parameters of glucose homeostasis were measured.

RESULTS

Cd accumulated in plasma, kidney and liver of rats exposed to 50 and 500 μg.kg.d, without inducing signs of organ failure. In rats drinking 5 μg.kg.d for 3 months, Cd exposure did not lead to any significant increase of Cd in these organs. At 50 and 500 μg.kg.d of Cd, glucose and insulin tolerance were unchanged in both sexes. However, females exhibited a significant increase of both fasting and glucose-stimulated plasma insulin that was assigned to impaired hepatic insulin extraction as indicated by unaltered fasting C-peptide plasma levels.

CONCLUSIONS

Glucose homeostasis is sensitive to chronic Cd exposure in a gender-specific way. Moreover, this study proves that an environmental pollutant such as Cd can have, at low concentrations, an impact on the glucose homeostatic system and it highlights the importance of a closer scrutiny of the underlying environmental causes to understand the increased incidence of type 2 diabetes.

摘要

背景

几项流行病学和动物研究表明,镉(Cd)暴露与 2 型糖尿病的发病率之间存在正相关,但这种相关性仍存在争议。此外,实验数据主要是在不同时期、通过相对较高水平的 Cd 和人工给药途径获得的。

目的

环境暴露于 Cd 是否会导致葡萄糖代谢明显紊乱?

方法

Wistar 大鼠暴露于饮用水中的 0、5、50 或 500μg.kg.d 的 CdCl3 中三个月。测量葡萄糖稳态的相关参数。

结果

暴露于 50 和 500μg.kg.d 的大鼠的血浆、肾脏和肝脏中积累了 Cd,但没有引起器官衰竭的迹象。在饮用 5μg.kg.d 的大鼠中,3 个月的 Cd 暴露并未导致这些器官中 Cd 的显著增加。在 50 和 500μg.kg.d 的 Cd 下,两性的葡萄糖和胰岛素耐量均未发生变化。然而,雌性表现出空腹和葡萄糖刺激的血浆胰岛素水平显著增加,这归因于肝胰岛素提取受损,如空腹 C 肽血浆水平不变所表明的那样。

结论

葡萄糖稳态对慢性 Cd 暴露具有性别特异性的敏感性。此外,本研究证明了一种环境污染物(如 Cd)即使在低浓度下也会对葡萄糖稳态系统产生影响,并强调了仔细研究潜在的环境原因对于理解 2 型糖尿病发病率增加的重要性。

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