Northern Medical Program, University of Northern British Columbia, Prince George, British Columbia, Canada.
J Toxicol Environ Health A. 2013;76(12):701-15. doi: 10.1080/15287394.2013.796503.
Evidence from recent epidemiological studies has emerged implicating exposure to environmental toxicants as a novel risk factor for the development of type 2 diabetes (T2D) and the metabolic syndrome in the general population. Humans and other organisms in high trophic levels of the food chain consume persistent organic pollutants (POP) through their diet. Few experimental studies demonstrating cause and effect are available and evidence for a direct association between accumulation of POP and T2D is preliminary; however, the possibility exists that lipophilic chemicals that accumulate in fatty tissue may disrupt cellular function and metabolic homeostasis. Chronic exposure of diabetes-prone C57B/6 mice to a polychlorinated biphenyl (PCB) mixture (Aroclor 1254, 36 mg/kg/wk, 20 wk) alone or in combination with high-fat diet impairs carbohydrate metabolism was compared to vehicle-treated control animals. Specifically, PBC exposure was found to produce hyperinsulinemia in both lean and diet-induced obese mice and exacerbated whole-body insulin resistance in obese mice. These changes in carbohydrate metabolism in response to Aroclor 1254 occurred without marked effect on body weight in both lean and obese mice. Our results demonstrate a causative association between PCB exposure and obesity-induced insulin resistance and hyperinsulinemia independent of body weight changes, an observation that contributes to a growing body of evidence suggesting that exposure to environmental pollutants represents a novel risk factor contributing to the diabetes epidemic.
最近的流行病学研究证据表明，暴露于环境毒物是普通人群中 2 型糖尿病（T2D）和代谢综合征发展的一个新的危险因素。食物链中营养级较高的人类和其他生物通过饮食摄入持久性有机污染物（POP）。目前仅有少数实验研究能够证明因果关系，并且 POP 与 T2D 之间存在直接关联的证据还很初步；然而，存在这样一种可能性，即蓄积在脂肪组织中的亲脂性化学物质可能会破坏细胞功能和代谢平衡。糖尿病易感 C57B/6 小鼠慢性暴露于多氯联苯（PCB）混合物（Aroclor 1254，36 mg/kg/周，20 周）中，单独或与高脂肪饮食联合使用，与接受载体处理的对照动物相比，会损害碳水化合物代谢。具体而言，发现 PCB 暴露会导致瘦鼠和饮食诱导肥胖鼠出现高胰岛素血症，并使肥胖鼠的全身胰岛素抵抗恶化。在瘦鼠和肥胖鼠中，Aroclor 1254 对碳水化合物代谢的这些变化与体重无明显影响。我们的研究结果表明，PCB 暴露与肥胖引起的胰岛素抵抗和高胰岛素血症之间存在因果关系，而与体重变化无关，这一观察结果为越来越多的证据提供了支持，即暴露于环境污染物是导致糖尿病流行的一个新的危险因素。
