Martin Elizabeth M, Stýblo Miroslav, Fry Rebecca C
Department of Environmental Sciences & Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Epigenomics. 2017 May;9(5):701-710. doi: 10.2217/epi-2016-0097. Epub 2017 May 4.
Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.
长期接触砷已被证实与糖尿病（DM）的发生有关，糖尿病是一种因葡萄糖稳态失调导致血糖升高为特征的疾病。本综述总结了砷诱导糖尿病的四种主要机制，即抑制胰岛素依赖的葡萄糖摄取、胰腺β细胞损伤、胰腺β细胞功能障碍以及刺激肝脏糖异生，体内和体外研究均支持这些机制。此外，还在砷相关糖尿病的背景下探讨了与砷毒性和疾病易感性相关的多态性变体的作用，以及与砷暴露相关的表观遗传修饰。综上所述，体外、体内以及人类遗传/表观遗传学研究均支持砷具有诱导糖尿病表型并损害参与葡萄糖稳态调节的关键途径的潜力。
