Ropero A B, Alonso-Magdalena P, García-García E, Ripoll C, Fuentes E, Nadal A
Instituto de Bioingeniería, Universidad Miguel Hernández de Elche, Alicante, Spain.
Int J Androl. 2008 Apr;31(2):194-200. doi: 10.1111/j.1365-2605.2007.00832.x. Epub 2007 Oct 31.
The link between endocrine disruptors and altered blood glucose homeostasis has been recently suggested. Epidemiological studies have correlated levels of phthalates, dioxins and persistent organic pollutants with alterations of blood glucose homeostasis in humans. Environmentally relevant doses of the ubiquitous endocrine disruptor bisphenol-A (BPA) have profound effects on mice endocrine pancreas--an essential tissue involved in glucose metabolism. BPA exerts rapid non-genomic effects on insulin releasing beta-cells and glucagon releasing alpha-cells within freshly isolated islets of Langerhans. In vivo, a single BPA injection of 10 microg/kg rapidly increases plasma insulin and concomitantly decreases glycaemia. When mice were treated with BPA 100 microg/kg/day for 4 days, the environmental oestrogen produced an increase in beta-cell insulin content along with a post-prandial hyperinsulinaemia and insulin resistance. The results reviewed here demonstrate that doses well below the current lowest observed adverse effect level considered by the US-EPA, disrupt pancreatic beta-cell function producing insulin resistance in male mice. Therefore, this altered blood glucose homeostasis by BPA exposure may enhance the risk of developing type II diabetes.
最近有研究表明内分泌干扰物与血糖稳态改变之间存在联系。流行病学研究已将邻苯二甲酸盐、二噁英和持久性有机污染物的水平与人类血糖稳态的改变联系起来。环境中普遍存在的内分泌干扰物双酚A(BPA)在与环境相关的剂量下,会对小鼠的内分泌胰腺产生深远影响,而内分泌胰腺是参与葡萄糖代谢的重要组织。BPA对新鲜分离的胰岛中释放胰岛素的β细胞和释放胰高血糖素的α细胞具有快速的非基因组效应。在体内,单次注射10微克/千克的BPA会迅速增加血浆胰岛素水平,并同时降低血糖水平。当小鼠以100微克/千克/天的剂量接受BPA处理4天时,这种环境雌激素会导致β细胞胰岛素含量增加,同时出现餐后高胰岛素血症和胰岛素抵抗。此处回顾的结果表明,在美国环境保护局(US-EPA)目前认为的最低观察到的有害作用水平之下的剂量,就会破坏胰腺β细胞功能,在雄性小鼠中产生胰岛素抵抗。因此,BPA暴露导致的这种血糖稳态改变可能会增加患II型糖尿病的风险。