Volatile anesthetics suppress glucose-stimulated insulin secretion in MIN6 cells by inhibiting glucose-induced activation of hypoxia-inducible factor 1.
Volatile anesthetics suppress glucose-stimulated insulin secretion in MIN6 cells by inhibiting glucose-induced activation of hypoxia-inducible factor 1.
复制标题
挥发性麻醉药通过抑制葡萄糖诱导的低氧诱导因子1的激活1。
作者：
Suzuki K;Sato Y;Kai S;Nishi K;Adachi T;Matsuo Y;Hirota K
合理的血糖控制是围手术期患者管理的重要目标之一。胰腺β细胞对血糖浓度升高的胰岛素分泌在血糖控制中起着最关键的作用。一些动物和人体研究表明，挥发性麻醉剂会损害葡萄糖刺激的胰岛素分泌(GSIS)。已经建立了一个令人信服的GSIS模型，在该模型中，细胞内ATP控制的依赖于ATP的钾通道(KATP)的活性起着关键作用。我们以前曾报道过葡萄糖刺激可导致缺氧诱导因子-1α(HIF-1α)加合物的形成和稳定化，并且高表达HIF-1α的MIN6细胞对葡萄糖诱导的缺氧具有抵抗力。基因消融HIF-1α或HIF-1β可显著抑制小鼠GSI。此外，我们在体外和体内都报道了挥发性麻醉剂抑制缺氧诱导的缺氧诱导的缺氧诱导因子的激活。为了研究挥发性麻醉剂对GSI的直接影响，我们使用了来源于小鼠胰腺β-细胞的MIN6细胞系。我们进行了一系列实验来检测挥发性麻醉剂(七氟醚和异氟醚)对GSIS的影响，结果表明，这些化合物抑制葡萄糖诱导的ATP升高，这依赖于细胞内低氧诱导的HIF-1活性，并在临床相关剂量下抑制GSIS。
Proper glycemic control is one of the most important goals in perioperative patient management. Insulin secretion from pancreatic β-cells in response to an increased blood glucose concentration plays the most critical role in glycemic control. Several animal and human studies have indicated that volatile anesthetics impair glucose-stimulated insulin secretion (GSIS). A convincing GSIS model has been established, in which the activity of ATP-dependent potassium channels (KATP) under the control of intracellular ATP plays a critical role. We previously reported that pimonidazole adduct formation and stabilization of hypoxia-inducible factor-1α (HIF-1α) were detected in response to glucose stimulation and that MIN6 cells overexpressing HIF-1α were resistant to glucose-induced hypoxia. Genetic ablation of HIF-1α or HIF-1β significantly inhibited GSIS in mice. Moreover, we previously reported that volatile anesthetics suppressed hypoxia-induced HIF activation in vitro and in vivo.To examine the direct effect of volatile anesthetics on GSIS, we used the MIN6 cell line, derived from mouse pancreatic β-cells. We performed a series of experiments to examine the effects of volatile anesthetics (sevoflurane and isoflurane) on GSIS and demonstrated that these compounds inhibited the glucose-induced ATP increase, which is dependent on intracellular hypoxia-induced HIF-1 activity, and suppressed GSIS at a clinically relevant dose in these cells.