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


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.


RESULTS
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 μM in the absence of anesthetic, and with propofol, and isoflurane, respectively. [ATP](i) and single K(ATP) channel conductance did not differ in islets exposed to isoflurane or propofol.


CONCLUSIONS
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.
Department of Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. katsuya@clin.med.tokushima-u.ac.jp
Katsuya
K
Tanaka
Takashi
T
Kawano
Yasuo M
YM
Tsutsumi
Michiko
M
Kinoshita
Nami
N
Kakuta
Kayo
K
Hirose
Masakazu
M
Kimura
Shuzo
S
Oshita
D000255:Adenosine Triphosphate / Q000032:analysis; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology*; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D007328:Insulin; D054086:KATP Channels; D000255:Adenosine Triphosphate; D007530:Isoflurane; D005947:Glucose; D015742:Propofol