Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine Reduction
Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine Reduction
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怀孕小鼠接触三氯生会通过甲状腺素减少导致胰岛素抵抗。
DOI：
10.1093/toxsci/kfx166
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发表时间：
2017-11-01
影响因子：
3.8
通讯作者：
Chen, Ling
中科院分区：
文献类型：
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作者：
Hua, Xu;Cao, Xin-Yuan;Chen, Ling
妊娠期间暴露于三氯生（TCS），一种抗菌剂，与甲状腺功能低下血症和胎盘葡萄糖转运蛋白表达和活性降低有关。本研究的目的是研究TCS对妊娠小鼠（g-小鼠）和非妊娠雌性小鼠（ng -小鼠）葡萄糖稳态和胰岛素敏感性的影响。本研究表明，从妊娠第5天（GD）到妊娠第17天，g -小鼠暴露于TCS （8 mg/kg）可显著增加其空腹血糖和血清胰岛素水平，以及胰腺β细胞胰岛素含量，降低稳态模型评估(HOMA)- β指数，增加HOMA- ir指数。TCS （8 mg/kg）处理的g -小鼠葡萄糖和胰岛素耐量试验曲线下面积（AUC）明显大于对照组。与对照组相比，TCS （8 mg/kg）处理的g -小鼠脂肪组织和肌肉中甲状腺素和三碘甲状腺原氨酸水平、PPAR γ和葡萄糖转运蛋白4 （GLUT4）表达以及Akt磷酸化水平均显著降低。在TCS （8 mg/kg）处理的g -小鼠中，l -甲状腺素的替代纠正了它们的胰岛素抵抗，并恢复了胰岛素水平、PPAR γ和GLUT4的表达以及Akt磷酸化。罗格列酮激活PPAR γ恢复了Akt磷酸化的下降，但没有恢复GLUT4的表达。虽然暴露于TCS （8 mg/kg）会降低ng小鼠的甲状腺激素水平，但不会引起胰岛素抵抗，也不会影响PPAR γ和GLUT4的表达以及Akt的磷酸化。研究结果表明，妊娠小鼠暴露于TCS （>= 8 mg/kg）通过甲状腺激素减少导致胰岛素抵抗。
Exposure to triclosan (TCS), an antibacterial agent, during pregnancy is associated with hypothyroxinemia and decreases in placental glucose transporter expression and activity. The objective of this study was to investigate the influence of TCS on glucose homeostasis and insulin sensitivity in gestational mice (G-mice) and nongestational female mice (Ng-mice) as a control. Herein, we show that the exposure of G-mice to TCS (8 mg/kg) from gestational day (GD) 5 to GD17 significantly increased their levels of fasting plasma glucose and serum insulin, and insulin content in pancreatic beta-cells with reduced homeostasis model assessment (HOMA)-beta index and increased HOMA-IR index. Area under curve (AUC) of glucose and insulin tolerance tests in TCS (8 mg/kg)-treated G-mice were markedly larger than controls. When compared with controls, TCS (8 mg/kg)-treated G-mice showed a significant decrease in the levels of thyroxine and triiodothyroninelevels, PPAR gamma and glucose transporter 4 (GLUT4) expression, and Akt phosphorylation in adipose tissue and muscle. Replacement of L-thyroxine in TCS (8 mg/kg)-treated G-mice corrected their insulin resistance and recovered the levels of insulin, PPAR gamma and GLUT4 expression, and Akt phosphorylation. Activation of PPAR gamma by administration of rosiglitazone recovered the decrease in Akt phosphorylation, but not GLUT4 expression. Although exposure to TCS (8 mg/kg) in Ng-mice reduced thyroid hormones levels, it did not cause the insulin resistance or affect PPAR gamma and GLUT4 expression, and Akt phosphorylation. The findings indicate that the exposure of gestational mice to TCS (>= 8 mg/kg) results in insulin resistance via thyroid hormones reduction.