Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
Sci Rep. 2018 Jan 15;8(1):772. doi: 10.1038/s41598-018-19260-x.
Olanzapine is a widely prescribed antipsychotic drug. While effective in reducing psychoses, treatment with olanzapine causes rapid increases in blood glucose. We wanted to determine if a single bout of exercise, immediately prior to treatment, would attenuate the olanzapine-induced rise in blood glucose and if this occurred in an IL-6 dependent manner. We found that exhaustive, but not moderate exercise, immediately prior to treatment, prevented olanzapine-induced hyperglycemia and this occurred in parallel with increases in serum IL-6. To determine if IL-6 was involved in the mechanisms through which exhaustive exercise protected against olanzapine-induced hyperglycemia several additional experiments were completed. Treatment with IL-6 (3 ng/g bw, IP) alone did not protect against olanzapine-induced increases in blood glucose. The protective effects of exhaustive exercise against olanzapine-induced increases in blood glucose were intact in whole body IL-6 knockout mice. Similarly, treating mice with an IL-6 neutralizing antibody prior to exhaustive exercise did not negate the protective effect of exercise against olanzapine-induced hyperglycemia. Our findings provide evidence that a single bout of exhaustive exercise protects against acute olanzapine-induced hyperglycemia and that IL-6 is neither sufficient, nor required for exercise to protect against increases in blood glucose with olanzapine treatment.
奥氮平是一种广泛应用的抗精神病药物。虽然它在降低精神病方面非常有效，但奥氮平的治疗会导致血糖迅速升高。我们想确定在治疗前进行一次单次运动是否会减轻奥氮平引起的血糖升高，以及这种作用是否依赖于白细胞介素 6（IL-6）。我们发现，在治疗前进行剧烈运动而非适度运动可以预防奥氮平引起的高血糖，并且这与血清 IL-6 的增加平行发生。为了确定白细胞介素 6 是否参与了剧烈运动防止奥氮平引起的高血糖的机制，我们完成了几项额外的实验。单独给予白细胞介素 6（3ng/g bw，腹腔注射）治疗并不能预防奥氮平引起的血糖升高。在全身白细胞介素 6 敲除小鼠中，剧烈运动对奥氮平引起的血糖升高的保护作用仍然存在。同样，在进行剧烈运动之前用白细胞介素 6 中和抗体处理小鼠也不会否定运动对奥氮平引起的高血糖的保护作用。我们的发现提供了证据表明，单次剧烈运动可以预防急性奥氮平引起的高血糖，并且白细胞介素 6 既不是剧烈运动预防奥氮平治疗引起的血糖升高所必需的，也不是充分的。
