State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China; Department of Earth Sciences, University of Oxford, Oxford OX1 3AN, United Kingdom.
State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China.
Toxicol Lett. 2018 Sep 15;294:87-94. doi: 10.1016/j.toxlet.2018.05.019. Epub 2018 May 16.
Epidemiological data from Lake Taihu showed significantly higher incidences of type 2 diabetes mellitus (T2DM) than in other areas of China. This may be related to the occurrence of a Microcystis bloom in Lake Taihu in the summer and autumn every year. The objective of this study is to investigate whether the contaminated water from the Microcystis bloom and the derivative pollutant microcystin-LR (MC-LR) can explain the higher incidences of T2DM. Healthy male mice were fed with water from different regions of Lake Taihu, and were either acutely or chronically exposed to MC-LR through oral administration or intraperitoneal injection. Serum lipid profiles were determined, and the effects on T2DM-related gene expression and insulin receptor signaling pathway were investigated. Intraperitoneal glucose tolerance (IPGTT) and insulin resistance (IRT) tests were implemented, and the functions of pancreatic islet and β-cell were also evaluated. The results showed that both water sampled from the region with a Microcysis bloom and those containing MC-LR altered the serum glucide and lipid profiles in mice after exposure. The exposure to a Microcysis bloom water affected the expression T2DM-related genes: up-regulated the mRNA levels of FASn, ACACA, G6pc, LPL, and Insig2, and down-regulated the mRNA level of PEPCK and Gsk-3β. Both acute and chronic exposure of MC-LR, even at very low concentrations (1 μg/L), impaired the insulin receptor signalling pathway and induced hyperinsulinemia and insulin resistance in mice. In this study, the most important intracellular target of MC-LR was found to be hetapocellular mitochondria. Thus, exposure to Microcystis bloom water containing microcystin-LR can induce the incidence of T2DM, by impairing the function of mitochondria by microcystin-LR. The study suggests a review of the risk assessment concerning 1 μg/L MC-LR as the reference dose in surface water.
太湖地区的流行病学数据显示,2 型糖尿病(T2DM)的发病率明显高于中国其他地区。这可能与每年夏季和秋季太湖蓝藻水华的发生有关。本研究旨在探讨蓝藻水华污染水及其衍生污染物微囊藻毒素-LR(MC-LR)是否可以解释 T2DM 发病率较高的原因。将健康雄性小鼠用来自太湖不同地区的水进行喂养,并通过口服或腹腔注射急性或慢性暴露于 MC-LR。测定血清脂质谱,并研究其对 T2DM 相关基因表达和胰岛素受体信号通路的影响。进行腹腔内葡萄糖耐量(IPGTT)和胰岛素抵抗(IRT)测试,并评估胰岛和β细胞的功能。结果表明,暴露于蓝藻水华区水样和含有 MC-LR 的水样均改变了暴露后小鼠的血清葡萄糖和脂质谱。暴露于蓝藻水华水样会影响 T2DM 相关基因的表达:上调 FASn、ACACA、G6pc、LPL 和 Insig2 的 mRNA 水平,下调 PEPCK 和 Gsk-3β 的 mRNA 水平。MC-LR 的急性和慢性暴露,即使在非常低的浓度(1μg/L)下,也会损害胰岛素受体信号通路,并导致小鼠发生高胰岛素血症和胰岛素抵抗。在本研究中,发现 MC-LR 的最重要的细胞内靶标是肝细胞线粒体。因此,暴露于含有微囊藻毒素-LR 的蓝藻水华污染水可通过微囊藻毒素-LR 损害线粒体功能来诱导 T2DM 的发生。该研究建议重新评估 1μg/L MC-LR 作为地表水参考剂量的风险评估。