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Voluntary physical activity protects against olanzapine-induced hyperglycemia
Journal of Applied Physiology ( IF 3.3 ) Pub Date : 2020-12-31 , DOI: 10.1152/japplphysiol.00876.2020 Hesham Shamshoum 1 , Greg L McKie 1 , Kyle D Medak 1 , Kristen E Ashworth 1 , Bruce E Kemp 2, 3 , David C Wright 1
Journal of Applied Physiology ( IF 3.3 ) Pub Date : 2020-12-31 , DOI: 10.1152/japplphysiol.00876.2020 Hesham Shamshoum 1 , Greg L McKie 1 , Kyle D Medak 1 , Kristen E Ashworth 1 , Bruce E Kemp 2, 3 , David C Wright 1
Affiliation
Olanzapine (OLZ) is used in the treatment of schizophrenia and a growing number of "off‐label" conditions. While effective in reducing psychoses, OLZ causes rapid impairments in glucose and lipid homeostasis. The purpose of this study was to investigate if voluntary physical activity via wheel running (VWR) would protect against the acute metabolic side effects of OLZ. Male C57BL/6J mice remained sedentary or were provided with running wheels overnight, prior to treatment with OLZ either at the beginning of the light cycle, or 7 or 24 hours following the cessation of VWR. Prior VWR protected against OLZ-induced hyperglycemia immediately and 7 hours following a bout of overnight wheel running. Protection against, hyperglycemia immediately following VWR was associated with increased insulin tolerance and an attenuated OLZ-induced increase in the serum glucagon:insulin ratio. The protective effect of VWR against OLZ-induced increases in hyperglycemia and glucagon:insulin ratio were maintained in high fat fed, and AMPK b1 deficient mice, models which display a potentiated OLZ-induced increase in blood glucose. Repeated OLZ treatment did not impair VWR performance and protection against the acute effects of OLZ on blood glucose was present after 1 week of daily OLZ treatment in mice given access to running wheels. In contrast to the effects on glucose metabolism, VWR, for the most part, did not impact OLZ induced perturbations in lipolysis, liver triglyceride accumulation or whole-body substrate oxidation. Collectively our findings demonstrate the efficacy of voluntary physical activity as an approach to protect against OLZ-induced impairments in glucose metabolism.
中文翻译:
自愿体育锻炼可预防奥氮平诱导的高血糖症
奥氮平(OLZ)用于治疗精神分裂症和越来越多的“标签外”疾病。OLZ虽然可以有效减少精神病,但会导致葡萄糖和脂质体内稳态迅速受损。这项研究的目的是调查通过滚轮行驶(VWR)进行的自愿体育锻炼是否可以预防OLZ的急性代谢副作用。雄性C57BL / 6J小鼠在光照周期开始时或在VWR停止后7或24小时内,在使用OLZ治疗之前,通常会久坐或在夜间提供跑轮。先前的VWR可立即和一整夜的车轮行驶7小时后防止OLZ引起的高血糖。防范,VWR后立即发生的高血糖与胰岛素耐受性增加和OLZ诱导的血清胰高血糖素:胰岛素比率增加相关。VWR对OLZ引起的高血糖症和胰高血糖素:胰岛素比率的保护作用在高脂喂养和AMPK b1缺陷小鼠中得以维持,这些模型显示了OLZ诱导的血糖升高。OLZ的重复治疗不会损害VWR的性能,并且在每天接受OLZ治疗的小鼠经过1周的转轮后,就可以防止OLZ对血糖的急性影响。与对葡萄糖代谢的影响相反,VWR在大多数情况下不影响OLZ在脂解,肝甘油三酸酯蓄积或全身底物氧化中引起的扰动。
更新日期:2021-01-01
中文翻译:
自愿体育锻炼可预防奥氮平诱导的高血糖症
奥氮平(OLZ)用于治疗精神分裂症和越来越多的“标签外”疾病。OLZ虽然可以有效减少精神病,但会导致葡萄糖和脂质体内稳态迅速受损。这项研究的目的是调查通过滚轮行驶(VWR)进行的自愿体育锻炼是否可以预防OLZ的急性代谢副作用。雄性C57BL / 6J小鼠在光照周期开始时或在VWR停止后7或24小时内,在使用OLZ治疗之前,通常会久坐或在夜间提供跑轮。先前的VWR可立即和一整夜的车轮行驶7小时后防止OLZ引起的高血糖。防范,VWR后立即发生的高血糖与胰岛素耐受性增加和OLZ诱导的血清胰高血糖素:胰岛素比率增加相关。VWR对OLZ引起的高血糖症和胰高血糖素:胰岛素比率的保护作用在高脂喂养和AMPK b1缺陷小鼠中得以维持,这些模型显示了OLZ诱导的血糖升高。OLZ的重复治疗不会损害VWR的性能,并且在每天接受OLZ治疗的小鼠经过1周的转轮后,就可以防止OLZ对血糖的急性影响。与对葡萄糖代谢的影响相反,VWR在大多数情况下不影响OLZ在脂解,肝甘油三酸酯蓄积或全身底物氧化中引起的扰动。