Volatile anesthetics suppress glucose-stimulated insulin secretion in MIN6 cells by inhibiting glucose-induced activation of hypoxia-inducible factor 1

Kengo Suzuki; Yoshifumi Sato; Shinichi Kai; Kenichiro Nishi; Takehiko Adachi; Yoshiyuki Matsuo; Kiichi Hirota

doi:10.7717/peerj.1498

Volatile anesthetics suppress glucose-stimulated insulin secretion in MIN6 cells by inhibiting glucose-induced activation of hypoxia-inducible factor 1

PeerJ. 2015 Dec 10:3:e1498. doi: 10.7717/peerj.1498. eCollection 2015.

Authors

Kengo Suzuki¹, Yoshifumi Sato², Shinichi Kai¹, Kenichiro Nishi¹, Takehiko Adachi³, Yoshiyuki Matsuo¹, Kiichi Hirota¹

Affiliations

¹ Department of Anesthesiology, Kansai Medical University , Hirakata, Osaka , Japan.
² Department of Medical Biochemistry, Faculty of Life Sciences, Kumamoto University , Kumamoto , Japan.
³ Department of Anesthesia, Tazuke Kofukai Medical Research Institute Kitano Hospital , Osaka , Japan.

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.

Keywords: ATP; HIF-1; Insulin secretion; MIN6 cell; Panreactic β-cell; Volatile anesthetic.

Grants and funding

This work was supported by JSPS KAKENHI Grant Number 24659695 and 22659283 to KH, to 25462457 to KN, and 24592322 and 15K10551 to TA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.