Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Universidad Miguel Hernández de Elche, Elche, Spain.
Environ Health Perspect. 2010 Sep;118(9):1243-50. doi: 10.1289/ehp.1001993. Epub 2010 May 7.
Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the base compound in the manufacture of polycarbonate plastics. In humans, epidemiological evidence has associated BPA exposure in adults with higher risk of type 2 diabetes and heart disease.
We examined the action of environmentally relevant doses of BPA on glucose metabolism in mice during pregnancy and the impact of BPA exposure on these females later in life. We also investigated the consequences of in utero exposure to BPA on metabolic parameters and pancreatic function in offspring.
Pregnant mice were treated with either vehicle or BPA (10 or 100 microg/kg/day) during days 9-16 of gestation. Glucose metabolism experiments were performed on pregnant mice and their offspring.
BPA exposure aggravated the insulin resistance produced during pregnancy and was associated with decreased glucose tolerance and increased plasma insulin, triglyceride, and leptin concentrations relative to controls. Insulin-stimulated Akt phosphorylation was reduced in skeletal muscle and liver of BPA-treated pregnant mice relative to controls. BPA exposure during gestation had long-term consequences for mothers: 4 months post-partum, treated females weighed more than untreated females and had higher plasma insulin, leptin, triglyceride, and glycerol levels and greater insulin resistance. At 6 months of age, male offspring exposed in utero had reduced glucose tolerance, increased insulin resistance, and altered blood parameters compared with offspring of untreated mothers. The islets of Langerhans from male offspring presented altered Ca2+ signaling and insulin secretion. BrdU (bromodeoxyuridine) incorporation into insulin-producing cells was reduced in the male progeny, yet beta-cell mass was unchanged.
Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and that BPA may be a risk factor for diabetes.
双酚 A（BPA）是一种广泛存在的内分泌干扰化学物质，用作制造聚碳酸酯塑料的基础化合物。在人类中，流行病学证据表明，成人接触 BPA 会增加患 2 型糖尿病和心脏病的风险。
我们研究了环境相关剂量的 BPA 对妊娠期间小鼠葡萄糖代谢的作用，以及 BPA 暴露对这些女性以后生活的影响。我们还研究了宫内暴露于 BPA 对后代代谢参数和胰腺功能的影响。
在妊娠第 9-16 天，用载体或 BPA（10 或 100μg/kg/天）处理怀孕的小鼠。对怀孕的小鼠及其后代进行葡萄糖代谢实验。
BPA 暴露加重了妊娠期间产生的胰岛素抵抗，与对照组相比，葡萄糖耐量降低，血浆胰岛素、甘油三酯和瘦素浓度增加。与对照组相比，BPA 处理的妊娠小鼠的骨骼肌和肝脏中胰岛素刺激的 Akt 磷酸化减少。BPA 暴露在妊娠期间对母亲有长期影响：产后 4 个月，治疗组的女性比未治疗组的女性体重更重，血浆胰岛素、瘦素、甘油三酯和甘油水平更高，胰岛素抵抗更大。6 个月时，宫内暴露的雄性后代的葡萄糖耐量降低，胰岛素抵抗增加，与未治疗母亲的后代相比，血液参数发生改变。雄性后代的胰岛呈现出改变的 Ca2+信号和胰岛素分泌。BrdU（溴脱氧尿苷）掺入产生胰岛素的细胞减少，但β细胞质量不变。
我们的研究结果表明，BPA 可能导致与葡萄糖稳态相关的代谢紊乱，并且 BPA 可能是糖尿病的一个危险因素。
