Huang Chun-Fa, Yang Ching-Yao, Chan Ding-Cheng, Wang Ching-Chia, Huang Kuo-How, Wu Chin-Ching, Tsai Keh-Sung, Yang Rong-Sen, Liu Shing-Hwa
School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
Environ Health Perspect. 2015 Nov;123(11):1138-44. doi: 10.1289/ehp.1408663. Epub 2015 Apr 10.
Epidemiological studies have reported that the prevalence of diabetes in women > 40 years of age, especially those in the postmenopausal phase, was higher than in men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose metabolism/homeostasis in the postmenopausal condition is still unclear.
We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice.
Adult female mice who underwent ovariectomy or sham surgery were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17β-estradiol supplementation for 2-6 weeks. Assays related to glucose metabolism were performed.
Exposure of sham mice to arsenic significantly increased blood glucose, decreased plasma insulin, and impaired glucose tolerance, but did not induce insulin resistance. Blood glucose and insulin were higher, and glucose intolerance, insulin intolerance, and insulin resistance were increased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Furthermore, liver phosphoenolpyruvate carboxykinase (PEPCK) mRNA expression was increased and liver glycogen content was decreased in arsenic-treated ovariectomized mice compared with arsenic-treated sham mice. Glucose-stimulated insulin secretion in islets isolated from arsenic-treated ovariectomized mice was also significantly decreased. Arsenic treatment significantly decreased plasma adiponectin levels in sham and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17β-estradiol supplementation.
Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females.
Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic exposure and glucose intolerance/insulin resistance in estrogen-deficient female mice. Environ Health Perspect 123:1138-1144; http://dx.doi.org/10.1289/ehp.1408663.
流行病学研究报告称，在饮用水砷含量高的地区，40岁以上女性，尤其是绝经后女性的糖尿病患病率高于男性。砷对绝经后状态下葡萄糖代谢/内稳态的具体影响仍不清楚。
我们研究了与人类饮用水暴露相关剂量的砷对雌激素缺乏雌性小鼠血糖调节的影响。
成年雌性小鼠接受卵巢切除术或假手术，在有或没有补充17β-雌二醇的情况下，饮用被三氧化二砷污染的水（0.05或0.5 ppm）2至6周。进行了与葡萄糖代谢相关的检测。
假手术小鼠暴露于砷会显著升高血糖、降低血浆胰岛素并损害葡萄糖耐量，但不会诱导胰岛素抵抗。与砷处理的假手术小鼠相比，砷处理的去卵巢小鼠血糖和胰岛素更高，葡萄糖不耐受、胰岛素不耐受和胰岛素抵抗增加。此外，与砷处理的假手术小鼠相比，砷处理的去卵巢小鼠肝脏磷酸烯醇丙酮酸羧激酶（PEPCK）mRNA表达增加，肝脏糖原含量降低。从砷处理的去卵巢小鼠分离的胰岛中葡萄糖刺激的胰岛素分泌也显著降低。砷处理显著降低了假手术和去卵巢小鼠的血浆脂联素水平。补充17β-雌二醇可逆转砷处理的去卵巢小鼠葡萄糖代谢/内稳态的改变。
我们的研究结果表明，雌激素缺乏在雌性小鼠砷改变的葡萄糖代谢/内稳态中起重要作用。
Huang CF, Yang CY, Chan DC, Wang CC, Huang KH, Wu CC, Tsai KS, Yang RS, Liu SH. 2015. Arsenic exposure and glucose intolerance/insulin resistance in estrogen-deficient female mice. Environ Health Perspect 123:1138-1144; http://dx.doi.org/10.1289/ehp.1408663.
