Kovács Diána, Hegedűs Csaba, Kiss Rita, Sári Réka, Németh József, Szilvássy Zoltán, Peitl Barna
Department of Pharmacology and Pharmacotherapy, University of Debrecen, Faculty of Medicine, Nagyerdei blvd. 98., Debrecen, 4032, Hungary.
Naunyn Schmiedebergs Arch Pharmacol. 2015 May;388(5):525-30. doi: 10.1007/s00210-015-1091-8. Epub 2015 Feb 3.
Olanzapine, an atypical antipsychotic, can acutely induce fasting insulin resistance, but we do not know whether it is able to modulate the meal-induced insulin sensitization (MIS). Two main experimental groups (control and olanzapine-treated) were created with two subgroups (fasted and re-fed) within each. After oral vehicle/olanzapine administration, the first meal size and duration and the total amount of consumed food was recorded in conscious rats. Then, under anaesthesia, the carotid artery and jugular vein was prepared and cannulated to obtain samples for blood glucose and hormone determination as well as for insulin/glucose infusion, respectively. Basal insulin sensitivity and MIS was determined by homeostasis model assessment (HOMA) calculation and by rapid insulin sensitivity test, respectively. In fasted animals, olanzapine increased blood glucose and plasma insulin and reduced basal insulin sensitivity, but it failed to modify other hormone levels. Postprandial leptin and glucose-dependent insulinotropic polypeptide (GIP) levels increased, and ghrelin level decreased significantly (p < 0.05) both in vehicle- and olanzapine-treated groups, but plasma insulin increased only in vehicle-treated animals. Furthermore, decrement in ghrelin level was attenuated in olanzapine-treated animals compared to controls. There was no significant change in the first meal size and duration or in the total amount of food consumed. Olanzapine had no effect on the MIS. We demonstrated that olanzapine can induce insulin resistance without weight gain in healthy rats. Furthermore, the MIS was preserved after acute olanzapine treatment. The blunted postprandial ghrelin and insulin response could contribute to the effect of olanzapine on feeding behaviour. Pharmacological induction of MIS may improve the olanzapine-induced insulin resistance.
奥氮平是一种非典型抗精神病药物，可急性诱导空腹胰岛素抵抗，但我们尚不清楚它是否能够调节餐后胰岛素敏感性（MIS）。实验分为两个主要组（对照组和奥氮平治疗组），每组又分为两个亚组（禁食组和再喂养组）。给清醒大鼠口服赋形剂/奥氮平后，记录首次进食的量和持续时间以及摄入食物的总量。然后，在麻醉状态下，准备并插管颈动脉和颈静脉，分别用于采集血糖和激素测定以及胰岛素/葡萄糖输注的样本。基础胰岛素敏感性和MIS分别通过稳态模型评估（HOMA）计算和快速胰岛素敏感性试验来确定。在禁食动物中，奥氮平可升高血糖和血浆胰岛素水平，并降低基础胰岛素敏感性，但未能改变其他激素水平。在赋形剂治疗组和奥氮平治疗组中，餐后瘦素和葡萄糖依赖性促胰岛素多肽（GIP）水平均升高，而胃饥饿素水平均显著降低（p < 0.05），但血浆胰岛素仅在赋形剂治疗的动物中升高。此外，与对照组相比，奥氮平治疗的动物胃饥饿素水平的降低有所减弱。首次进食的量和持续时间或摄入食物的总量没有显著变化。奥氮平对MIS没有影响。我们证明，奥氮平可在健康大鼠中诱导胰岛素抵抗而不导致体重增加。此外，急性奥氮平治疗后MIS得以保留。餐后胃饥饿素和胰岛素反应减弱可能有助于奥氮平对进食行为的影响。MIS 的药理学诱导可能改善奥氮平诱导的胰岛素抵抗。
