title: Arsenic Exposure and Glucose Intolerance/Insulin Resistance in Estrogen-Deficient Female Mice.
abstract: 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.
  
  
  OBJECTIVE
  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 arsenic-altered glucose metabolism/homeostasis in females.
  
  
  BACKGROUND
  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.
authors: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors: Chun-Fa
authors: CF
authors: Huang
authors: Ching-Yao
authors: CY
authors: Yang
authors: Ding-Cheng
authors: DC
authors: Chan
authors: Ching-Chia
authors: CC
authors: Wang
authors: Kuo-How
authors: KH
authors: Huang
authors: Chin-Ching
authors: CC
authors: Wu
authors: Keh-Sung
authors: KS
authors: Tsai
authors: Rong-Sen
authors: RS
authors: Yang
authors: Shing-Hwa
authors: SH
authors: Liu
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001786:Blood Glucose / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D018149:Glucose Intolerance / Q000139:chemically induced*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D051379:Mice; D010052:Ovariectomy
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D001786:Blood Glucose; D004967:Estrogens; D007328:Insulin; D004958:Estradiol; D001151:Arsenic