Edwards Joshua, Ackerman Christopher
Department of Pharmacology, Midwestern University, Downers Grove, IL 60515, USA.
Curr Diabetes Rev. 2016;12(3):252-8. doi: 10.2174/1573399811666150812142922.
There is increasing interest in how exposure to environmental substances can contribute to the onset of Type II diabetes mellitus (T2DM). Impaired insulin release is a hallmark of type I diabetes mellitus and is involved in the progression of T2DM. Both epidemiological and experimental studies show that exposure to the environmental pollutant cadmium (Cd), is associated with hyperglycemia, T2DM and reduced serum insulin. The goal of this review is to examine likely mechanisms of action of Cd-induced dysglycemia based on experimental studies in the literature and from the most recent findings in the Edwards lab. The primary focus of this review will examine how Cd may cause islet dysfunction and subsequent impaired insulin release. Recent findings in the Edwards lab indicate that Cd causes timedependent and statistically significant changes in fasting leptin, Glucose-dependent Insulinotropic Polypeptide (GIP) and pancreas polypeptide hormone levels in a subchronic animal model of Cd-induced hyperglycemia. This review summarizes the most likely cellular mechanisms by which the ubiquitous environmental contaminant Cd disrupts glucose homeostasis. While individual cellular effects of Cd are reviewed it is likely that no one single mechanism is involved, rather multiple mechanisms exist and work synergistically resulting in islet dysfunction and ultimately dysglycemia.
环境物质暴露如何导致II型糖尿病（T2DM）发病受到越来越多的关注。胰岛素释放受损是I型糖尿病的一个标志，并与T2DM的进展有关。流行病学和实验研究均表明，接触环境污染物镉（Cd）与高血糖、T2DM及血清胰岛素降低有关。本综述的目的是基于文献中的实验研究以及爱德华兹实验室的最新发现，探讨镉诱导血糖异常的可能作用机制。本综述的主要重点将是研究镉如何导致胰岛功能障碍以及随后的胰岛素释放受损。爱德华兹实验室的最新发现表明，在镉诱导高血糖的亚慢性动物模型中，镉会导致空腹瘦素、葡萄糖依赖性促胰岛素多肽（GIP）和胰腺多肽激素水平随时间发生有统计学意义的变化。本综述总结了普遍存在的环境污染物镉破坏葡萄糖稳态最可能的细胞机制。虽然文中回顾了镉对细胞的个体影响，但可能并非单一机制起作用，而是存在多种机制并协同发挥作用，导致胰岛功能障碍并最终引发血糖异常。
