Department of Occupational Health and Environmental Health, School of Public Health, Capital Medical University, Beijing, 100069, China.
Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, Beijing, 100069, China.
Environ Sci Pollut Res Int. 2024 Feb;31(6):8952-8962. doi: 10.1007/s11356-023-31772-2. Epub 2024 Jan 6.
Methyl tert-butyl ether (MTBE), a type of gasoline additive, has been found to affect insulin function and glucose homeostasis in animal experiments, but there is still no epidemiological evidence. Zinc (Zn) is a key regulatory element of insulin secretion and function, and Zn homeostasis can be disrupted by MTBE exposure through inducing oxidative stress. Therefore, we suspected that Zn might be involved and play an important role in the process of insulin secretion inhibited by MTBE exposure. In this study, we recruited 201 male subjects including occupational and non-occupational MTBE exposure from Anhui Province, China in 2019. Serum insulin and functional analog fibroblast growth factor 1 (FGF1) and blood MTBE were detected by Elisa and headspace solid-phase microextraction and gas chromatography-high-resolution mass spectrometry. According to MTBE internal exposure level, the workers were divided into low- and high-exposed groups and found that the serum insulin level in the high-exposed group was significantly lower than that in the low-exposed group (p = 0.003) while fasting plasma glucose (FPG) level increased obviously in the high-exposed group compared to the low-exposed group (p = 0.001). Further analysis showed that MTBE exposure level was positively correlated with FPG level, but negatively correlated with serum insulin level, which suggested that the FPG level increase might be related to the decrease of serum insulin level induced by MTBE exposure. The results of further mediation effect analysis showed that changes in serum zinc levels played a major intermediary role in the process of insulin secretion inhibition and blood glucose elevation caused by MTBE exposure. In addition, a significant negative correlation was found between MTBE exposure and serum Zn level, which might play a strong mediating effect on the inhibition of insulin secretion induced by MTBE exposure. In conclusion, our study provided evidence that MTBE could inhibit insulin secretion and interfere with Zn metabolism in gas station workers for the first time, and found that Zn might play an important mediation effect during the process of inhibiting insulin secretion and interfering with glucose metabolism induced by MTBE exposure.
甲基叔丁基醚（MTBE）是一种汽油添加剂，在动物实验中已发现其会影响胰岛素功能和葡萄糖稳态，但目前仍缺乏流行病学证据。锌（Zn）是胰岛素分泌和功能的关键调节元素，而 MTBE 暴露通过诱导氧化应激会破坏 Zn 稳态。因此，我们怀疑 Zn 可能参与并在 MTBE 暴露抑制胰岛素分泌的过程中发挥重要作用。在这项研究中，我们于 2019 年在中国安徽省招募了 201 名男性受试者，包括职业和非职业 MTBE 暴露者。通过酶联免疫吸附试验和顶空固相微萃取与气相色谱-高分辨率质谱法检测血清胰岛素和功能模拟成纤维细胞生长因子 1（FGF1）和血液 MTBE。根据 MTBE 内部暴露水平，将工人分为低暴露组和高暴露组，发现高暴露组的血清胰岛素水平明显低于低暴露组（p=0.003），而高暴露组的空腹血糖（FPG）水平明显高于低暴露组（p=0.001）。进一步分析表明，MTBE 暴露水平与 FPG 水平呈正相关，与血清胰岛素水平呈负相关，这表明 FPG 水平的升高可能与 MTBE 暴露引起的血清胰岛素水平降低有关。进一步的中介效应分析结果表明，血清锌水平的变化在 MTBE 暴露引起的胰岛素分泌抑制和血糖升高过程中起主要中介作用。此外，还发现 MTBE 暴露与血清 Zn 水平呈显著负相关，这可能对 MTBE 暴露引起的胰岛素分泌抑制有很强的中介作用。总之，我们的研究首次提供了证据表明 MTBE 可以抑制加油站工人的胰岛素分泌并干扰锌代谢，并且发现 Zn 可能在 MTBE 暴露引起的胰岛素分泌抑制和葡萄糖代谢干扰过程中发挥重要的中介作用。
