title: Long-term oral exposure to bisphenol A induces glucose intolerance and insulin resistance.
abstract: Bisphenol A (BPA) is a widely used endocrine disruptor. Recent epidemiologic results have suggested an association between exposure to BPA and cardiovascular disease, type 2 diabetes, and obesity. We investigated the in vivo effects of long-term oral exposure to BPA on insulin resistance and glucose intolerance. In the present study, 4- to 6-week-old male mice on a high-fat diet (HFD) were treated with 50 μg/kg body weight per day of BPA orally for 12 weeks. Long-term oral exposure to BPA along with an HFD for 12 weeks induced glucose intolerance in growing male mice. Intraperitoneal glucose tolerance tests showed that the mice that received an HFD and BPA exhibited a significantly larger area under the curve than did those that received an HFD only (119.9±16.8 vs. 97.9±18.2 mM/min, P=0.027). Body weight, percentage of white adipose tissue, and percentage of body fat did not differ between the two groups of mice. However, treatment with BPA reduced Akt phosphorylation at position Thr308 and GSK3β phosphorylation at position Ser9 in skeletal muscle. BPA tended to decrease serum adiponectin levels and to increase serum interleukin 6 and tumor necrosis factor α, although these findings were not statistically significant. Treatment with BPA did not induce any detrimental changes in the islet area or morphology or the insulin content of β cells. In conclusion, long-term oral exposure to BPA induced glucose intolerance and insulin resistance in growing mice. Decreased Akt phosphorylation in skeletal muscle by way of altered serum adipocytokine levels might be one mechanism by which BPA induces glucose intolerance.
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Min Kyong
authors.initials: MK
authors.lastname: Moon
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: In-Kyong
authors.initials: IK
authors.lastname: Jeong
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Tae
authors.initials: T
authors.lastname: Jung Oh
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Hwa Young
authors.initials: HY
authors.lastname: Ahn
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Hwan Hee
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea yjparkmd@snu.ac.kr.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Hak Chul
authors.initials: HC
authors.lastname: Jang
authors.affiliation: Department of Internal MedicineSeoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Republic of KoreaDepartment of Internal MedicineBoramae Medical Center, Seoul 156-707, Republic of KoreaDepartment of Internal MedicineChung-Ang University Hospital, College of Medicine, Chung-Ang University, Seoul 156-755, Republic of KoreaClinical Research InstituteSeoul National University Hospital, Seoul 110-74, Republic of KoreaDepartment of Internal MedicineSeoul National University Bundang Hospital, Seongnam 463-707, Republic of Korea.
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000633:toxicity*; D059305:Diet, High-Fat / Q000009:adverse effects; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity; D018149:Glucose Intolerance / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D007328:Insulin; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: adipocytokine; bisphenol A; glucose intolerance; insulin resistance; skeletal muscle