Differential effects of propofol and isoflurane on glucose utilization and insulin secretion.
Differential effects of propofol and isoflurane on glucose utilization and insulin secretion.
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DOI：
10.1016/j.lfs.2010.10.032
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发表时间：
2011-01
期刊：
影响因子：
6.1
通讯作者：
Katsuya Tanaka;T. Kawano;Y. Tsutsumi;Michiko Kinoshita;N. Kakuta;Kayo Hirose;M. Kimura;S. Oshita
中科院分区：
文献类型：
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作者：
Katsuya Tanaka;T. Kawano;Y. Tsutsumi;Michiko Kinoshita;N. Kakuta;Kayo Hirose;M. Kimura;S. Oshita
目的挥发性麻醉剂，如异氟烷，逆转葡萄糖诱导的胰腺三磷酸腺苷敏感性钾（KATP）通道活性抑制，导致胰岛素分泌减少和葡萄糖耐量受损。以前没有研究过静脉麻醉剂（如丙泊酚）对胰腺KATP通道的影响。本研究探讨了异氟醚和异丙酚对胰腺ATP通道和胰岛素分泌的影响及其细胞机制。胰岛从雄性大鼠中分离，并用于灌流研究，测量细胞内ATP浓度（[ATP]i），和膜片钳experiments.Key FindingsGlucose刺激显着增加胰岛素分泌异丙酚麻醉期间，但不是异氟烷麻醉，在IVGTT研究。在灌注实验中，暴露于丙泊酚的胰岛和未暴露于麻醉剂的对照胰岛对高剂量的葡萄糖有双相胰岛素分泌反应。然而，异氟烷显著抑制葡萄糖诱导的胰岛素分泌。在膜片钳研究中，ATP浓度和通道活性之间的关系可以通过Hill方程拟合，在无麻醉剂、丙泊酚和异氟烷的情况下，半最大抑制分别为22.4、15.8和218.8μM。[ATP] i和单个KATP通道电导在暴露于异氟醚或丙泊酚的胰岛中没有差异。显著性我们的结果表明，异氟醚，而不是丙泊酚，降低了KATP通道的ATP敏感性，损害了葡萄糖刺激的胰岛素释放。异氟醚和丙泊酚对ATP敏感性的不同作用可以解释异氟醚和丙泊酚对胰岛素释放的不同作用。
AIMSVolatile anesthetics, such as isoflurane, reverse glucose-induced inhibition of pancreatic adenosine triphosphate-sensitive potassium (KATP) channel activity, resulting in reduced insulin secretion and impaired glucose tolerance. No previous studies have investigated the effects of intravenous anesthetics, such as propofol, on pancreatic KATPchannels. We investigated the cellular mechanisms underlying the effects of isoflurane and propofol on pancreatic KATPchannels and insulin secretion.MAIN METHODSIntravenous glucose tolerance tests (IVGTT) were performed on male rabbits. Pancreatic islets were isolated from male rats and used for a perifusion study, measurement of intracellular ATP concentration ([ATP]i), and patch clamp experiments.KEY FINDINGSGlucose stimulus significantly increased insulin secretion during propofol anesthesia, but not isoflurane anesthesia, in IVGTT study. In perifusion experiments, both islets exposed to propofol and control islets not exposed to anesthetic had a biphasic insulin secretory response to a high dose of glucose. However, isoflurane markedly inhibited glucose-induced insulin secretion. In a patch clamp study, the relationship between ATP concentration and channel activity could be fitted by the Hill equation with a half-maximal inhibition of 22.4, 15.8, and 218.8μM in the absence of anesthetic, and with propofol, and isoflurane, respectively. [ATP]iand single KATPchannel conductance did not differ in islets exposed to isoflurane or propofol.SIGNIFICANCEOur results indicate that isoflurane, but not propofol, decreases the ATP sensitivity of KATPchannels and impairs glucose-stimulated insulin release. These differential actions of isoflurane and propofol on ATP sensitivity may explain the differential effects of isoflurane and propofol on insulin release.