Promoting insulin secretion in pancreatic islets by means of bisphenol A and nonylphenol via intracellular estrogen receptors.
In this study, we investigated the effects of endocrine disrupters bisphenol A (BPA) and nonylphenol (NP) on insulin secretion from rat pancreatic islets. Following acute exposure to BPA and NP, neither BPA nor NP (0.1, 1, 10, 100 and 1000 microg/l) affected insulin secretion in concentrations of 16.7 mM glucose. However, insulin secretion following long-term exposure to BPA or NP for 24 h in 16.7 mM glucose was significantly higher than without exposure. To determine whether increased insulin secretion resulting from long-term exposure to BPA and NP is induced via intracellular estrogen receptors, we blocked the cytosolic/nuclear estrogen receptors, using actinomycin-D (Act-D), an inhibitor of RNA synthesis, and ICI 182,780 (ICI), an estrogen receptor inhibitor. Following long-term exposure to BPA (10 microg/l) or NP (10 microg/l), Act-D or ICI treatment eliminated the facilitation of insulin secretion. In conclusion, we have demonstrated for the first time that long-term exposure to endocrine disrupters, such as BPA and NP, promotes in vitro insulin secretion from the pancreatic islets, via cytosolic/nuclear estrogen receptors.
Adachi
Tetsuya
T
Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan. adachi@tom.life.h.kyoto-u.ac.jp
Yasuda
Koichiro
K
Mori
Chisato
C
Yoshinaga
Mariko
M
Aoki
Norihiko
N
Tsujimoto
Gozoh
G
Tsuda
Kinsuke
K
D000818:Animals; D001559:Benzhydryl Compounds; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D000077267:Fulvestrant; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010636:Phenols / Q000494:pharmacology*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D003609:Dactinomycin; D004958:Estradiol; D004965:Estrogen Antagonists; D004968:Estrogens, Non-Steroidal; D000077267:Fulvestrant; D005947:Glucose; D007328:Insulin; D010636:Phenols; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C025256:nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds