Differential effects of propofol and isoflurane on glucose utilization and insulin secretion

作者：Tanaka Katsuya^*; Kawano Takashi; Tsutsumi Yasuo M; Kinoshita Michiko; Kakuta Nami; Hirose Kayo; Kimura Masakazu; Oshita Shuzo

来源：Life Sciences, 2011, 88(1-2): 96-103.

DOI：10.1016/j.lfs.2010.10.032

• Isoflurane
• Propofol
• K(ATP) channels
• Insulin secretion
• Pancreatic beta-cells

Aims: Volatile anesthetics, such as isoflurane, reverse glucose-induced inhibition of pancreatic adenosine triphosphate-sensitive potassium (K(ATP)) 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 K(ATP) channels. We investigated the cellular mechanisms underlying the effects of isoflurane and propofol on pancreatic K(ATP) channels and insulin secretion.
Main methods: Intravenous 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 findings: Glucose 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 218.8 mu M in the absence of anesthetic, and with propofol, and isoflurane, respectively. [ATP], and single K(ATP) channel conductance did not differ in islets exposed to isoflurane or propofol.
Significance: Our results indicate that isoflurane, but not propofol, decreases the ATP sensitivity of K(ATP) channels 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.

• 出版日期2011-1-3