Clozapine-Induced Acute Hyperglycemia Is Accompanied with Elevated Serum Concentrations of Adrenaline and Glucagon in Rats
Clozapine-Induced Acute Hyperglycemia Is Accompanied with Elevated Serum Concentrations of Adrenaline and Glucagon in Rats
复制标题
DOI：
10.1248/bpb.b18-00195
复制
发表时间：
2018-08-01
影响因子：
2
通讯作者：
Yasuhara, Masato
中科院分区：
文献类型：
--
作者：
Nagata, Masashi;Kimura, Yuri;Yasuhara, Masato
氯氮平是一种非典型的抗精神病药物，据报道可引起急性高血糖。然而，氯氮平诱导的快速发展的高血糖症的机制还没有很好地阐明。为了阐明氯氮平引起急性高血糖的机制，我们研究了单次静脉注射氯氮平对大鼠血清葡萄糖和几种内源性物质浓度的影响。雄性Wistar大鼠静脉注射生理盐水（对照）或氯氮平2.5、5、10 mg/kg。氯氮平给药后定期采集血样，测定血糖、肾上腺素、胰高血糖素、胰岛素、皮质酮和氯氮平的血清浓度。氯氮平2.5 - 10mg/kg剂量组血糖、肾上腺素和胰高血糖素浓度呈剂量依赖性升高，5mg/kg剂量组达到最高。血皮质酮浓度随氯氮平剂量的增加而升高，但无显著性差异。血清胰岛素浓度在服用氯氮平后呈剂量依赖性升高。总之，氯氮平单次给药可增加大鼠血清葡萄糖浓度，肾上腺素和/或胰高血糖素与氯氮平诱导的急性高血糖症相关。
Clozapine, an atypical antipsychotic agent, has been reported to cause acute hyperglycemia. However, the mechanism of clozapine-induced rapidly developing hyperglycemia is not well elucidated. To clarify the mechanism underlying clozapine-induced acute hyperglycemia, we investigated the effects of single intravenous administration of clozapine on the serum concentrations of glucose and several endogenous substances in rats. Male Wistar rats received an intravenous injection of saline (control) or clozapine 2.5, 5, 10 mg/kg. Blood samples were obtained periodically after clozapine administration to determine the serum concentrations of glucose, adrenaline, glucagon, insulin, corticosterone, and clozapine. The serum concentrations of glucose, adrenaline, and glucagon increased dose-dependently after the administration of clozapine at 2.5-10mg/kg, and reached maxima at 5mg/kg of clozapine. The serum concentration of corticosterone increased after the administration of clozapine, but no significant variation was observed with the dosage of clozapine. The concentration of serum insulin increased in a dose-dependent manner after clozapine administration. In conclusion, a single administration of clozapine increased the serum concentration of glucose in rats, and adrenaline and/or glucagon would be associated with clozapine-induced acute hyperglycemia.