A strong correlation between chronic arsenic exposure and neuropsychological disorders leads to a growing concern about a potential risk of arsenic related neurodegeneration. Evidently, brain insulin signaling contributes to physiological effects, including energy homeostasis, and learning and memory. Arsenic has been shown to impair insulin signaling in adipocytes and myocytes, however, this impairment has not yet been explored in neurons. Here we showed that NaAsO₂ caused significant reduction in basal levels of glucose, plasma membrane glucose transporter, GLUT 3 and Akt phosphorylation in differentiated human neuroblastoma SH-SY5Y cells. NaAsO₂ significantly decreased insulin-mediated glucose uptake, as well as GLUT1 and 3 membrane translocation. Furthermore, the ability of insulin to increase Akt phosphorylation, a well-recognized insulin signaling response, was significantly lessened by NaAsO₂ treatment. In addition, the classical tyrosine phosphorylation response of insulin was reduced by NaAsO₂, as evidenced by reduction of insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1(IRS-1). Moreover, NaAsO₂ lowered the ratio of p110, a catalytic subunit to p85, a regulatory subunit of PI3K causing an imbalance between p110 and p85, the conditions reported to contribute to insulin sensitivity. Additionally, increment of IRS-1 interaction with GSK3β, and p85-PI3K were observed in NaAsO₂ treated cells. These molecular modulations may be mechanistically attributed to neuronal insulin signaling impairment by arsenic.

慢性砷暴露与神经心理疾病之间的密切相关性导致人们越来越担心砷相关的神经变性的潜在风险。显然，脑胰岛素信号传导有助于生理作用，包括能量稳态，学习和记忆。砷已显示会损害脂肪细胞和肌细胞中的胰岛素信号传导，但是，这种损伤尚未在神经元中进行研究。在这里，我们表明，NaAsO ₂导致分化的人神经母细胞瘤SH-SY5Y细胞的基础葡萄糖水平，质膜葡萄糖转运蛋白，GLUT 3和Akt磷酸化水平显着降低。NaAsO ₂显着降低胰岛素介导的葡萄糖摄取以及GLUT1和3膜移位。此外，NaAsO ₂处理显着降低了胰岛素增强Akt磷酸化（公认的胰岛素信号转导反应）的能力。此外，NaAsO ₂降低了胰岛素的经典酪氨酸磷酸化反应，这可以通过降低胰岛素诱导的胰岛素受体（IR）和胰岛素受体底物-1（IRS-1）的酪氨酸磷酸化来证明。此外，NaAsO ₂降低了导致p110和p85不平衡的PI3K催化亚基p110与p85调节亚基p85的比例，据报道，这种情况有助于胰岛素敏感性。此外，在NaAsO ₂处理的细胞中观察到IRS-1与GSK3β和p85-PI3K相互作用的增加。这些分子调节可能在机理上归因于砷引起的神经元胰岛素信号转导障碍。