Mechanisms of Impaired Glucose Tolerance and Insulin Secretion during Isoflurane Anesthesia.
Tanaka, Katsuya M.D. *; Kawano, Takashi M.D. +; Tomino, Takehito B.S. ++; Kawano, Hiroaki M.D. [S]; Okada, Tsuyoshi M.D. [S]; Oshita, Shuzo M.D. [//]; Takahashi, Akira M.D. #; Nakaya, Yutaka M.D. **
111(5):1044-1051, November 2009.
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Background: Volatile anesthetics impair insulin secretion and glucose utilization; however, the precise mechanism of action that underlies these effects is unknown. The authors hypothesized that isoflurane inhibits glucose-induced inhibition of adenosine triphosphate-sensitive potassium channel activity in pancreatic [beta] cells, which could result in impaired insulin secretion and glucose tolerance.
Methods: Intravenous glucose tolerance tests were performed on 28 male Japanese White rabbits anesthetized with sodium pentobarbital. Glibenclamide (50 [mu]g/kg 33.5 [mu]g [middle dot] kg-1 [middle dot] h-1) or vehicle was administered 75 min before intravenous administration of 0.6 g/kg glucose. Half of the animals (n = 7) in the vehicle and glibenclamide groups received isoflurane at 1.0 minimum alveolar concentration 30 min before administration of glucose, and the other half received a vehicle control. Hemodynamics, blood glucose, and plasma insulin were measured. A cell-attached patch clamp configuration was used to record single channel currents in the pancreas from male Swiss-Webster mice.
Results: Isoflurane alone or a combination of isoflurane and glibenclamide inhibited the insulinogenic index to a greater extent than in the vehicle and glibenclamide groups. In the patch clamp experiments, channel activity was significantly decreased as the glucose concentration was increased from 0 to 10 mm. The subsequent application of 0.5 mm isoflurane reversed the effects of glucose on channel activity.
Conclusion: These results show that isoflurane impairs insulin secretion and glucose utilization. The mechanism of action responsible for these effects may involve a decrease in glucose-induced inhibition of adenosine triphosphate-sensitive potassium channel activity in pancreatic [beta] cells.
(C) 2009 American Society of Anesthesiologists, Inc.