The glucose tolerance test in mice: Sex, drugs and protocol.
The glucose tolerance test in mice: Sex, drugs and protocol.
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DOI：
10.1111/dom.14811
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发表时间：
2022-11
影响因子：
5.8
通讯作者：
King, Aileen J.
中科院分区：
文献类型：
--
作者：
Kennard, Matilda R.;Nandi, Manasi;Chapple, Sarah;King, Aileen J.
关键词：
旨在确定性别、给药途径、禁食持续时间和急性习惯应激对用于潜在葡萄糖调节疗法临床前评估的葡萄糖耐量试验（GTT）测量的影响。植入 HD-XG 葡萄糖遥测装置的成年雄性和雌性 C57Bl/6J 小鼠在由于整个笼子更换、笼子更换保留用过的垫料或在腹膜内 (IP) GTT 之前不更换笼子而导致急性习惯应激后禁食 16 小时或 6 小时。为了评估方案的完善和性别对 GTT 检测药物作用的能力的影响，我们使用优化方案给予 250 mg/kg 口服二甲双胍或 10 nmol/kg IP exendin-4。雌性小鼠在开始禁食时对人类干预不太敏感。禁食 6 小时后，保留垫料并更换笼底可促进两性基础血糖更快稳定。长时间禁食 16 小时会导致 GTT 反应过度，但会引起明显的基础低血糖。 GTT 方案优化后，exendin-4 和二甲双胍的效果在两性中是相同的，女性表现出更温和但更可重复的 GTT 反应。 GTT 方案的变化对葡萄糖稳态具有深远影响。方案的改进和/或使用女性仍然可以检测药物效应，提供证据表明更严重的表型并不是表征/验证新药的必要先决条件。
To establish the impact of sex, dosing route, fasting duration and acute habituation stress on glucose tolerance test (GTT) measurements used in the preclinical evaluation of potential glucose‐modulating therapeutics. Adult male and female C57Bl/6J mice, implanted with HD‐XG glucose telemetry devices, were fasted for 16 hours or 6 hours following acute habituation stress due to whole cage change, cage change with retention of used bedding or no cage change prior to intraperitoneal (IP) GTTs. To evaluate protocol refinement and sex on the ability of the GTT to detect drug effects, we administered 250 mg/kg oral metformin or 10 nmol/kg IP exendin‐4 using optimized protocols. Female mice were less sensitive to human intervention when initiating fasting. Following a 6‐hour fast, retention of bedding whilst changing the cage base promotes quicker stabilization of basal blood glucose in both sexes. Prolonged fasting for 16 hours resulted in an exaggerated GTT response but induced pronounced basal hypoglycaemia. Following GTT protocol optimization the effect of exendin‐4 and metformin was equivalent in both sexes, with females showing a more modest but more reproducible GTT response. Variations in GTT protocol have profound effects on glucose homeostasis. Protocol refinement and/or the use of females still allows for detection of drug effects, providing evidence that more severe phenotypes are not an essential prerequisite when characterizing/validating new drugs.
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影响因子：
20.3
作者：
Kautzky-Willer A;Harreiter J;Pacini G
通讯作者：
Pacini G
影响因子：
2.9
作者：
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Corssmit, EPM
DOI：
10.1152/ajpendo.90617.2008
发表时间：
2008-12-01
影响因子：
5.1
作者：
Andrikopoulos, Sofianos;Blair, Amy R.;Proietto, Joseph
通讯作者：
Proietto, Joseph
影响因子：
4.8
作者：
Kaikaew, Kasiphak;Steenbergen, Jacobie;Visser, Jenny A.
通讯作者：
Visser, Jenny A.