目的 观察奥氮平对雄性小鼠能量消耗和糖代谢的影响及可能机制。方法 将10 只C57BL/6J 雄性小鼠随机分为两组，分别奥氮平及其溶剂灌胃2 周，观察小鼠摄食、体质量、空腹血糖、糖耐量和胰岛素耐量的变化，监测24 h 能量代谢，并比较肝脏糖代谢相关基因的表达。结果 小鼠奥氮平给药后出现胰岛素抵抗和高血糖；白天能量消耗明显下降，呼吸商趋势性下降，氧化底物由葡萄糖向脂肪转移；肝内糖异生关键酶磷酸烯醇式丙酮酸羟激酶（PEPCK）和葡萄糖-6-磷酸酶（G-6-pase）的基因表达明显升高。结论 奥氮平诱导的高血糖可不依赖于摄食和体质量增加；奥氮平可直接诱导胰岛素抵抗并促进肝糖异生。
Mechanism of olanzapine-induced energy imbalance and glucose metabolism disorder in C57BL/6Jmale mice
Objective To study the effects and mechanism of olanzapine on energy consumptionand glucose metabolism in male mice. Methods Ten C57BL/6J male mice were randomly divided into twogroups. The mice in two groups were given olanzapine or its solvent by gavage separately for 2 weeks. Food intake,body weight, fasting blood glucose, glucose tolerance and insulin tolerance were recorded. Energy consumption of 24 h was monitored. And expressions of hepatic glucose metabolism related genes were compared. Results After administration of olanzapine for two weeks, insulin resistance and hyperglycemia were observed, oxygenand energy consumptions were significantly decreased during the daytime, and respiratory exchange ratio showed a downward trend which indicated that the oxidized substrates were transferred from glucose to fat. And mRNA levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-pase) were significant-ly increased. Conclusions Olanzapine-induced hyperglycemia may not dependent on hyperphagia and weight gain. Olanzapine can directly induce insulin resistance and promote hepatic gluconeogenesis.