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BACKGROUND: The incidence of low birth weights is increased in offspring of women who are exposed to high concentrations of arsenic in drinking water compared with other women. We hypothesized [...]

BACKGROUND: 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. OBJECTIVES: We investigated the effects of arsenic at doses relevant to human exposure from drinking water on blood glucose regulation in estrogen-deficient female mice. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our findings suggest that estrogen deficiency plays an important role in arsenicaltered glucose metabolism/homeostasis in females. http://dx.doi.org/10.1289/ehp.1408663, Introduction Arsenic is a naturally occurring toxic metalloid. Levels of naturally occurring arsenic in groundwater above the drinking water standard of 10 µg/L are not uncommon. Several studies in Taiwan [...]