Mechanisms of impaired glucose tolerance and insulin secretion during isoflurane anesthesia.
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 microg/kg + 33.5 microg x kg x h) 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.


CONCLUSIONS
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.
Tanaka
Katsuya
K
Department of Anesthesiology, Tokushima University School of Medicine, Japan. katsuya@clin.med.tokushima-u.ac.jp
Kawano
Takashi
T
Tomino
Takehito
T
Kawano
Hiroaki
H
Okada
Tsuyoshi
T
Oshita
Shuzo
S
Takahashi
Akira
A
Nakaya
Yutaka
Y
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D018149:Glucose Intolerance / Q000139:chemically induced*; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000494:pharmacology; D006439:Hemodynamics; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007530:Isoflurane / Q000494:pharmacology*; D054086:KATP Channels / Q000187:drug effects; D008297:Male; D051379:Mice; D011817:Rabbits
D018685:Anesthetics, Inhalation; D001786:Blood Glucose; D007328:Insulin; D054086:KATP Channels; D007530:Isoflurane; D005905:Glyburide; D002118:Calcium