不那么快:在持续监测葡萄糖的小鼠中,由于食物撤回,葡萄糖耐受性测试的变异性矛盾地增加了
William B Rubio1, Marissa D Cortopassi1, Deepti Ramachandran1
1Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.
Molecular metabolism
|August 28, 2023
概括
在葡萄糖耐受性测试之前禁食小鼠可以悖论地增加变异性. 短暂的禁食会引起压力,而长时间的禁食会导致昏迷,这既会扭曲结果,又会影响葡萄糖代谢.
科学领域:
- 代谢研究研究 代谢研究
- 动物模型 动物模型
- 临床前研究 临床前研究
背景情况:
- 禁食通常用于临床前动物模型,以减少代谢参数的个体间变化.
- 个体在养行为上的变化需要禁食来进行代谢和行为实验.
- 禁食引起的压力可能会扭曲实验变量,包括葡萄糖耐受性测试 (GTT) 的结果.
研究的目的:
- 为了确定禁食时间对小鼠葡萄糖耐受性测试 (GTT) 复制性的影响.
- 在临床前模型中调查禁食如何影响葡萄糖代谢和动物间的变异性.
- 评估禁食引起的压力和生理状态对GTT反应的影响.
主要方法:
- 在成年雄性小鼠中使用了4周的同时持续血糖监测 (CGM) 和间接热量计.
- 数量化血糖,体力活动,体温,新陈代谢率和每分钟的食物消耗.
- 在光/黑暗光周期期间,在GTT上测试了4小时或18小时的禁食效果,有或没有CGM.
主要成果:
- 在光明时期的4小时禁食,矛盾地增加了动物之间的代谢率,活性,温度和葡萄糖耐受性的变化.
- 这种高血糖和高代谢的表型与皮质的增加相关,表明对食物剥夺的压力反应.
- 一个18小时快速诱导的,以低体温和代谢率为特征,与显著降低的葡萄糖水平,影响GTT反应.
结论:
- 在葡萄糖耐受性测试前禁食小鼠可以增加实验变异性,这与预期的效果相反.
- 短期禁食引起的压力和长期禁食引起的麻木都会对GTT的可重现性产生负面影响.
- 这些发现建议重新考虑GTT和其他临床前实验的禁食协议,以避免引入偏见.
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