Department of Endocrinology, Dr. A.L.M Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Department of Endocrinology, Dr. A.L.M Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600 113, India.
Chem Biol Interact. 2017 Nov 1;277:119-128. doi: 10.1016/j.cbi.2017.09.003. Epub 2017 Sep 11.
Chromium (Cr), an essential micronutrient potentiates insulin action, whereas excess hexavalent Cr (CrVI) acts as an endocrine disruptor. Pregnant mothers living in areas abutting industries using the metal and chromite ore dumps are exposed to ground water contaminated with Cr. Nevertheless, the impact of prenatal exposure to excess CrVI on insulin signaling in the progeny remains obscure. We tested the hypothesis "transient gestational exposure to drinking water containing excess CrVI may modify insulin signaling during postnatal life". Pregnant Wistar rats were given drinking water containing 50, 100 and 200 ppm CrVI (KCrO) from gestational day 9-14 encompassing the period of organogenesis; the male progenies were tested at postnatal day 60. Neither fasting blood glucose nor oral glucose tolerance was altered in CrVI treated progeny. Nevertheless, western blot detection pointed out attenuated expression level of insulin receptor (IR), its downstream signaling molecules (IRS-1, pIRS-1, Akt and pAkt) and organ specific glucose transporters (GLUT2 in liver and GLUT4 in gastrocnemius muscle), along with a significant increase in serum insulin level in male progenies exposed to CrVI. While C-2-deoxy glucose uptake increased in the liver, the same decreased in the skeletal muscle whereas, C-glucose oxidation recorded a consistent decrease in both tissues of CrVI exposed rats. These findings support our hypothesis and suggest that transient gestational exposure to excess CrVI may affect insulin signaling and glucose oxidation in the progeny, predictably rendering them vulnerable to insulin resistance.
铬（Cr）是一种必需的微量元素，能增强胰岛素的作用，而过量的六价铬（CrVI）则作为一种内分泌干扰物。居住在毗邻使用该金属和铬铁矿堆的工业的孕妇会接触到受 Cr 污染的地下水。然而，产前暴露于过量 CrVI 对后代胰岛素信号的影响仍不清楚。我们检验了“短暂的妊娠期暴露于含有过量 CrVI 的饮用水可能会改变后代生命后期的胰岛素信号”这一假说。从胚胎发生期的第 9-14 天起，给怀孕的 Wistar 大鼠提供含有 50、100 和 200 ppm CrVI（KCrO）的饮用水；雄性后代在出生后第 60 天进行测试。CrVI 处理的后代的空腹血糖或口服葡萄糖耐量均未改变。然而，Western blot 检测表明，胰岛素受体（IR）及其下游信号分子（IRS-1、pIRS-1、Akt 和 pAkt）和组织特异性葡萄糖转运体（肝脏中的 GLUT2 和腓肠肌中的 GLUT4）的表达水平降低，同时血清胰岛素水平显著升高在暴露于 CrVI 的雄性后代中。虽然 C-2-脱氧葡萄糖摄取在肝脏中增加，但在骨骼肌中则减少，而 C-葡萄糖氧化在暴露于 CrVI 的大鼠的两种组织中都持续减少。这些发现支持我们的假说，并表明短暂的妊娠期暴露于过量的 CrVI 可能会影响后代的胰岛素信号和葡萄糖氧化，使他们容易发生胰岛素抵抗。
