The Involvement of Adenosine Triphosphate-Sensitive Potassium Channels in the Different Effects of Sevoflurane and Propofol on Glucose Metabolism in Fed Rats

Abstract

Recently, we reported marked differences in the effects of sevoflurane and propofol on glucose metabolism; glucose use is impaired by sevoflurane, but not by propofol. Opening of adenosine triphosphate-sensitive potassium channels (K(ATP) channels) in β islet cells attenuates insulin secretion, while inhibition of K(ATP) channels in β islet cells increases insulin secretion. It is reported that volatile anesthetics open K(ATP) channels, whereas propofol inhibits K(ATP) channels. In this study, we examined the effects of sevoflurane and propofol on glucose metabolism under normovolemic and hypovolemic conditions, focusing on insulin secretion. Anesthesia was induced with sevoflurane (3% in 1 L/min oxygen) in all rats. After surgical preparation, rats were assigned to 2 groups. Anesthesia was maintained with sevoflurane (2% in 1 L/min oxygen) in the 1st group, and with propofol (a bolus dose of 30 mg/kg followed by continuous infusion at a rate of 30 mg · kg(-1) · h(-1)) in the 2nd group. Each group was divided into 3 subgroups: rats without pretreatment, rats pretreated with glibenclamide, and rats pretreated with nicorandil. After a 30-minute stabilization period, we withdrew 15 mL/kg of blood to induce hypovolemia. We evaluated glucose metabolism under both normovolemic and hypovolemic conditions by measuring blood glucose levels and plasma insulin levels. Under both normovolemia and hypovolemia, glucose levels in rats anesthetized with sevoflurane were significantly higher than those in rats anesthetized with propofol, and insulin levels in rats anesthetized with sevoflurane were significantly lower than those in rats anesthetized with propofol. Glibenclamide, a K(ATP) channel inhibitor, significantly decreased glucose levels and significantly increased insulin levels under sevoflurane anesthesia, suggesting that sevoflurane decreases insulin secretion by opening K(ATP) channels in β islet cells. Glibenclamide significantly decreased glucose levels and significantly increased insulin levels under propofol anesthesia as well; however, insulin levels in rats pretreated with glibenclamide under propofol anesthesia were much higher than those in rats pretreated with glibenclamide under sevoflurane anesthesia. Furthermore, insulin levels in rats without pretreatment under propofol anesthesia seemed to be equal to or higher than those in rats pretreated with glibenclamide under sevoflurane anesthesia. These results suggest that there are marked differences in the effects of sevoflurane and propofol on insulin secretion regulated by K(ATP) channels in β islet cells. Nicorandil, a K(ATP) channel opener, produced no significant effects on glucose metabolism under both sevoflurane and propofol anesthesia. Insulin secretion regulated by K(ATP) channels in β islet cells is involved, at least in part, in the different effects of sevoflurane and propofol on glucose metabolism.