Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.
Low doses of bisphenol A and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclassical membrane estrogen receptor within intact islets of Langerhans.
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DOI：
10.1289/ehp.8002
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发表时间：
2005-08
影响因子：
10.4
通讯作者：
Nadal A
中科院分区：
文献类型：
--
作者：
Alonso-Magdalena P;Laribi O;Ropero AB;Fuentes E;Ripoll C;Soria B;Nadal A
胰高血糖素由整合在胰岛内的胰腺α细胞分泌，通过增强肝脏中葡萄糖的合成和动员参与葡萄糖代谢的调节。此外，它还具有其他肝外效应，从脂肪组织中的脂解作用到中枢神经系统中的饱腹感控制。在这篇文章中，我们发现内分泌干扰物双酚A（BPA）和己烯雌酚（DES）在浓度为10−9 M时，抑制了低葡萄糖诱导的α细胞内钙离子（[Ca 2 +]i）振荡，这是触发胰高血糖素分泌的信号。这种作用具有快速起效，并且通过结合辣根过氧化物酶（E-HRP）的不可渗透分子雌二醇（E2）来复制。在免疫细胞化学鉴定的α-细胞中使用E-HRP结合的竞争研究表明，17β-E2、BPA和DES共享一个共同的膜结合位点，其药理学特征不同于经典的ER。BPA、DES和E2引发的效应可被Gαi和Gα o蛋白抑制剂百日咳毒素、鸟苷酸环化酶特异性抑制剂1H-[1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮和一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯阻断。该作用可通过8-溴-鸟苷3′，5 ′-环一磷酸重现，并在cGMP依赖性蛋白激酶抑制剂KT-5823存在下受到抑制。E2、BPA和DES在胰腺α-细胞中的作用可以解释内分泌干扰物在糖和脂质代谢中引起的一些效应。
Glucagon, secreted from pancreatic α-cells integrated within the islets of Langerhans, is involved in the regulation of glucose metabolism by enhancing the synthesis and mobilization of glucose in the liver. In addition, it has other extrahepatic effects ranging from lipolysis in adipose tissue to the control of satiety in the central nervous system. In this article, we show that the endocrine disruptors bisphenol A (BPA) and diethylstilbestrol (DES), at a concentration of 10−9 M, suppressed low-glucose–induced intracellular calcium ion ([Ca2+]i) oscillations in α-cells, the signal that triggers glucagon secretion. This action has a rapid onset, and it is reproduced by the impermeable molecule estradiol (E2) conjugated to horseradish peroxidase (E-HRP). Competition studies using E-HRP binding in immunocytochemically identified α-cells indicate that 17β-E2, BPA, and DES share a common membrane-binding site whose pharmacologic profile differs from the classical ER. The effects triggered by BPA, DES, and E2 are blocked by the Gαi- and Gαo-protein inhibitor pertussis toxin, by the guanylate cyclase–specific inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one, and by the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. The effects are reproduced by 8-bromo-guanosine 3′,5′-cyclic monophosphate and suppressed in the presence of the cGMP-dependent protein kinase inhibitor KT-5823. The action of E2, BPA, and DES in pancreatic α-cells may explain some of the effects elicited by endocrine disruptors in the metabolism of glucose and lipid.
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影响因子：
10.4
作者：
Frigo, Daniel E;Burow, Matthew E;Mitchell, Kamron A;Chiang, Tung-Chin;McLachlan, John A
通讯作者：
McLachlan, John A
肾上腺素通过增加 Ca2+ 电流和靠近 L 型 Ca2+ 通道的颗粒数量来刺激胰腺 A 细胞的胰高血糖素分泌。
影响因子：
3.8
作者：
Gromada, J;Bokvist, K;Ding, WG;Barg, S;Buschard, K;Renstrom, E;Rorsman, P
通讯作者：
Rorsman, P
DOI：
10.1016/s0960-0760(02)00261-3
发表时间：
2002-12-01
影响因子：
4.1
作者：
Cardona-Gómez, GP;Mendez, P;Garcia-Segura, LM
通讯作者：
Garcia-Segura, LM
影响因子：
2.7
作者：
Guillette, LJ;Pickford, DB;Percival, HF
通讯作者：
Percival, HF
影响因子：
4
作者：
Åkesson, B;Henningsson, R;Lundquist, I
通讯作者：
Lundquist, I