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

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 insulin-resistant 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 pre-treatment.

Lean and obese male C57BL/6J mice were anesthetized with sevoflurane for 60 min with or without pre-treatment of 62.5 mg·kg^-1 salsalate. Blood glucose, plasma insulin, and glucose uptake into different tissues were measured.

Under sevoflurane anesthesia, obese mice had higher blood glucose compared to lean mice. Increases in blood glucose were attenuated with acute salsalate pre-treatment 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 µmol·g^-1 tissue·hr^-1; P < 0.001).

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.