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ANESTHETIC PHARMACOLOGY

Sevoflurane Increases Glucose Transport in Skeletal Muscle Cells

Akira Kudoh, MD^*, Hiroshi Katagai, MD, and Tomoko Takazawa, MD

*Department of Anesthesiology, University of Hirosaki School of Medicine; and Department of Anesthesiology, Hirosaki National Hospital, Hirosaki, Aomori, Japan

Address correspondence and reprint requests to Akira Kudoh, MD, Department of Anesthesiology, Hirosaki National Hospital, 1 Tominocho, Hirosaki 036-8545, Aomori, Japan.

Sevoflurane activates phospholipase C and protein kinase C, leading to an increase in intracellular Ca²⁺ concentration, which modulates glucose transport. We studied in vitro the effect of sevoflurane on the uptake of 2-deoxyglucose in rat skeletal muscle cells and the mechanism that modulates the glucose transport. Sevoflurane 0.8, 1.2, and 2.0 mM significantly increased glucose uptake from 13.1 ± 1.2 pmol · h^-1 · mg protein^-1 to 22.6 ± 1.4, 32.1 ± 1.8, and 37.4 ±2.7 pmol · h^-1 · mg protein^-1, respectively. Tyrphostin A-23 (a highly selective tyrosine kinase inhibitor) 1 and 10 nM significantly decreased the sevoflurane-stimulated glucose uptake from 32.1 ± 1.8 to 25.8 ± 1.1 and 15.2 ± 1.7 pmol · h^-1 · mg protein^-1, respectively. Genistein (a selective tyrosine kinase inhibitor) 1 and 10 nM also significantly decreased the sevoflurane- stimulated glucose uptake from 32.1 ± 1.8 to 25.7 ± 1.5 and 15.2 ± 1.4 pmol · h^-1 · mg protein^-1, respectively. The sevoflurane-stimulated glucose uptake was decreased by 100 nM and 1 µM TMB-8 (an intracellular Ca²⁺ antagonist), from 32.1 ± 1.8 pmol · h^-1 · mg protein^-1 to 25.6 ± 3.3 and 20.3 ± 1.6 pmol · h^-1 · mg protein^-1, respectively. Staurosporine (a protein kinase C antagonist) 100 nM significantly decreased sevoflurane-stimulated glucose uptake to 26.1 ± 1.5 pmol · h^-1 · mg protein^-1. We conclude that sevoflurane increases glucose uptake in skeletal muscle cells and that the sevoflurane-stimulated glucose uptake was associated with tyrosine kinase, protein kinase C, and intracellular Ca²⁺.

IMPLICATIONS: Sevoflurane anesthesia has an inhibitory effect on insulin secretion. Glucose concentrations in plasma do not significantly change during sevoflurane anesthesia. Plasma glucose concentrations are affected by intracellular glucose metabolism. However, glucose transport into cells during sevoflurane anesthesia remains unclear.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999