Evidence for functional nicotinic receptors on pancreatic β cells
Evidence for functional nicotinic receptors on pancreatic β cells
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DOI：
10.1016/j.metabol.2004.08.020
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发表时间：
2005-02-01
影响因子：
9.8
通讯作者：
Grill, V
中科院分区：
文献类型：
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作者：
Yoshikawa, H;Hellström-Lindahl, E;Grill, V
流行病学研究将吸烟与胰岛素分泌减少联系起来。我们假设尼古丁会对胰腺 β 细胞功能产生负面影响。急性或48小时接触尼古丁（10（-4）至10（-6）mol/L）会中度抑制大鼠和人胰岛的基础（3.3 mmol/L）和/或升高（27 mmol/L）葡萄糖水平的胰岛素释放。急性接触尼古丁 (10-6 mol/L) 可抑制甲苯磺丁脲 (200 μmol/L) 诱导的胰岛素释放 41% (P < .05)，但不影响 KCl (20 mmol/L) 或 3-异丁基-1-甲基黄嘌呤 (1 mmol/L) 诱导的分泌（在大鼠胰岛中测试）。 [H-3]尼古丁的特异性结合在大鼠胰岛和大鼠来源的β细胞系INS-1中得到证实。与尼古丁(10(-7)mol/L)共培养48小时可增强这种结合。通过逆转录酶聚合酶链反应检测 INS-1 细胞中烟碱受体亚基 α2、α3、α4、α5、α7 和 β2 mRNA 的表达。急性暴露于α4、β2亚基激动剂金雀花碱(10(-6)mol/L)可部分抑制甲苯磺丁脲诱导的胰岛素释放。可以在 INS-1 细胞中证明 1 个金环蛇毒素 (10(-10) mol/L)（a7 亚基的拮抗剂）的特异性结合，并且在基础葡萄糖和升高葡萄糖的培养后孵育中，用金环蛇毒素进行培养会适度增加胰岛素释放，P < 0.05。我们的数据表明功能性烟碱受体存在于胰岛和β细胞中。 (C) 2005 Elsevier Inc. 保留所有权利。
Epidemiological studies associate smoking with reduced insulin secretion. We hypothesized that nicotine could negatively affect pancreatic beta-cell function. Acute or 48-hour exposures to nicotine (10(-4) to 10(-6) mol/L) moderately inhibited insulin release at basal (3.3 mmol/L) and/or elevated (27 mmol/L) glucose in rat and human islets. Acute exposure to nicotine (10-6 mol/L) inhibited tolbutamide (200 mumol/L)-induced insulin release by 41% (P < .05), but did not affect secretion induced by KCl (20 mmol/L) or 3-isobutyl-1-methylxanthine (1 mmol/L) (tested in rat islets). Specific binding of [H-3]nicotine was demonstrated in rat islets and in a beta-cell line of rat origin, INS-1. Such binding was enhanced by 48 hours of coculture with nicotine (10(-7) mol/L). Expression of mRNA for the nicotinic receptor subunits alpha2, alpha3, alpha4, alpha5, alpha7, and beta2 was detected in INS-1 cells by reverse transcriptase polymerase chain reaction. Acute exposure to cytisine (10(-6) mol/L), an agonist of alpha4, beta2 subunits, partially inhibited tolbutamide-induced insulin release. Specific binding of 1 bungarotoxin (10(-10) mol/L), an antagonist of the a7 subunit, could be demonstrated in INS-1 cells, and culture with a bungarotoxin modestly increased insulin release in postculture incubations at basal and elevated glucose, P < .05. Our data indicate that functional nicotinic receptors are present in pancreatic islets and beta cells. (C) 2005 Elsevier Inc. All rights reserved.