Sevoflurane-induced hyperglycemia is attenuated by salsalate in obese insulin-resistant mice

Abstract

Purpose Perioperative hyperglycemia is common and is associated with significant morbidity. Although patient characteristics and surgery influence perioperative glucose metabolism, anesthetics have a significant impact. We hypothesized that mice that were obese and insulinresistant would experience greater hyperglycemia in response to sevoflurane anesthesia compared with lean controls. We further hypothesized that sevoflurane-induced hyperglycemia would be attenuated by salsalate pretreatment. Methods Lean and obese male C57BL/6J mice were anesthetized with sevoflurane for 60 min with or without pre-treatment of 62.5 mgÁkg -1 salsalate. Blood glucose, plasma insulin, and glucose uptake into different tissues were measured. Results Under sevoflurane anesthesia, obese mice had higher blood glucose compared to lean mice. Increases in blood glucose were attenuated with acute salsalate pretreatment at 60 min under anesthesia in obese mice (mean ± standard error of the mean [SEM], delta blood glucose; vehicle 5.79 ± 1.09 vs salsalate 1.91 ± 1.32 mM; P = 0.04) but did not reach statistical significance in lean mice (delta blood glucose, vehicle 4.39 ± 0.55 vs salsalate 2.79 ± 0.71 mM; P = 0.10). This effect was independent of changes in insulin but associated with an approx. 1.7-fold increase in glucose uptake into brown adipose tissue (vehicle 45.28 ± 4.57 vs salsalate 76.89 ± 12.23 lmolÁg -1 tissueÁhr -1 ; P \ 0.001). Conclusion These data show that salsalate can reduce sevoflurane-induced hyperglycemia in mice. This indicates that salsalate may represent a new class of therapeutics that, in addition to its anti-inflammatory and analgesic properties, may be useful to reduce perioperative hyperglycemia. Re ´sumeÓbjectif L'hyperglyce´mie pe´riope´ratoire est fre´quente et est associe´e a `une morbidite´significative. Bien que les caracte´ristiques propres au patient et a`la chirurgie influencent le me´tabolisme pe´riope´ratoire du glucose, les anesthe´siques ont un impact significatif. Nous avons e´mis l'hypothe`se que l'hyperglyce´mie en re´ponse a`une anesthe´sie a`base de se´voflurane serait plus prononce´e