Dynamics of blood glucose changes and hormonal sensitivity under anesthesia with medetomidine-midazolam-butorphanol...

Recent trends in laboratory animal research have shifted the anesthetic choice as a result of concerns about safety, animal welfare, and regulatory issues. Consequently, rodent studies have widely adopted the combination of medetomidine, midazolam, and butorphanol (MMB). Although studies have reported that MMB anesthesia elevates blood glucose levels, the time-dependent changes in blood glucose and the responsiveness to hormones involved in glucose regulation have not been sufficiently investigated. This study aimed to clarify the temporal profile of blood glucose levels under MMB anesthesia and evaluate the responsiveness to adrenaline and insulin, representative hormones that influence glucose levels. Beginning 10 min after administration, MMB anesthesia induced a marked increase in blood glucose levels, and the elevation persisted up to 60 min. In contrast, pentobarbital anesthesia produced only a transient and mild increase, with no changes observed in the saline group. Blood glucose levels increased under awake and pentobarbital-anesthetized conditions in response to adrenaline, but exhibited no change under MMB anesthesia. In streptozotocin-induced hyperglycemic rats, the glucose-lowering effect of insulin was observed to a similar extent under awake, pentobarbital-anesthetized, and MMB-anesthetized conditions. The present results show that MMB anesthesia has a marked effect on blood glucose levels and alters the response to adrenaline. Therefore, in experiments that measure physiological or biochemical parameters under anesthesia, it is necessary to carefully consider the potential influence of MMB anesthesia on experimental outcomes and critically evaluate the appropriateness of its use.