Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice

Background: Epidemiological studies reported that the prevalence of diabetes in women over 40 years of age, especially those in the postmenopausal phase, was higher than men in areas with high levels of arsenic in drinking water. The detailed effect of arsenic on glucose meta bolism/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 were exposed to drinking water contaminated with arsenic trioxide (0.05 or 0.5 ppm) in the presence or absence of 17 beta-estradiol supplementation for 2-6 weeks . Assays related to glucose metabolism were performed. Results : Exposure of normal 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 was increased in ovariectomized mice compared with sham-control mice treated with arsenic. Furthermore, liver phosphoenolpyruvate carboxykinase mRNA expression was increased and liver glycogen content was decreased in ovariectomized mice compared with controls treated with arsenic. 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-control and ovariectomized mice. Altered glucose metabolism/homeostasis in arsenic-treated ovariectomized mice was reversed by 17 beta-estradiol supplementation. Conclusions: Our findings suggest that estrogen deficiency plays an important role in arsenic-altered glucose metabolism/homeostasis in females.