title: Volatile anesthetics suppress glucose-stimulated insulin secretion in MIN6 cells by inhibiting glucose-induced activation of hypoxia-inducible factor 1.
abstract: 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 (K ATP) 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.
authors.affiliation: Department of Anesthesiology, Kansai Medical University , Hirakata, Osaka , Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University , Kumamoto , Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sato
authors.affiliation: Department of Anesthesiology, Kansai Medical University , Hirakata, Osaka , Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kai
authors.affiliation: Department of Anesthesiology, Kansai Medical University , Hirakata, Osaka , Japan.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Nishi
authors.affiliation: Department of Anesthesia, Tazuke Kofukai Medical Research Institute Kitano Hospital , Osaka , Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Anesthesiology, Kansai Medical University , Hirakata, Osaka , Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Matsuo
authors.affiliation: Department of Anesthesiology, Kansai Medical University , Hirakata, Osaka , Japan.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Hirota
keywords: ATP; HIF-1; Insulin secretion; MIN6 cell; Panreactic β-cell; Volatile anesthetic