The intravenous glucose tolerance test in cannulated Wistar rats:: A robust method for the in vivo assessment of glucose-stimulated insulin secretion
The intravenous glucose tolerance test in cannulated Wistar rats:: A robust method for the in vivo assessment of glucose-stimulated insulin secretion
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DOI：
10.1016/j.vascn.2007.12.002
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发表时间：
2008-03-01
影响因子：
1.9
通讯作者：
Poucher, Simon M.
中科院分区：
文献类型：
--
作者：
Frangioudakis, Georgia;Gyte, Amie C.;Poucher, Simon M.
简介：葡萄糖刺激的胰岛素分泌（GSIS）对于哺乳动物燃料稳态至关重要，并且在β细胞功能障碍的早期演变中减少，最终导致2型糖尿病的发展。我们试图验证和验证静脉内葡萄糖耐量试验（IVGTT），一种常用的技术，以评估GSIS，在麻醉和清醒插管雄性汉Wistar大鼠。方法：雄性Han Wistar大鼠经右颈静脉和左颈动脉插管。麻醉和长期插管清醒模型使用增加剂量的葡萄糖（0.2、0.5和1.0 g葡萄糖/kg LBM）或在接受0.5 g葡萄糖/kg LBM推注剂量之前用Exendin-4（EX-4）预处理后进行IVGTT。在整个实验的时间点测量血糖、血浆胰岛素和血浆C肽。结果如下：在麻醉和清醒插管大鼠中，静脉注射葡萄糖推注剂量增加后，观察到血糖、胰岛素和C肽（测量值）呈剂量依赖性增加。0.5 g葡萄糖/kg LBM推注导致中等反应，并用于研究的第二部分。EX-4预处理与葡萄糖组合导致GSIS增强，如通过单独的血浆胰岛素测量（麻醉模型）或胰岛素和C肽测量（清醒模型）所评估的。讨论内容：通过进行葡萄糖剂量反应研究，在麻醉和清醒插管的雄性Han Wistar大鼠中对IVGTT进行标准化，并通过使用EX-4检查GSIS增强进行验证。基于这些结果，推荐0.5 g葡萄糖/kg LBM推注剂量作为在具有增强葡萄糖敏感性胰腺功能潜力的新化合物的任何标准化筛选阶段评估GSIS的剂量。这些研究中描述的实验条件可以转移到疾病模型中，以更详细地评估新化合物的功效。(c)2008年爱思唯尔公司All rights reserved.
Introduction: Glucose-stimulated insulin secretion (GSIS) is critical in mammalian fuel homeostasis and is diminished early in the evolution of beta-cell dysfunction, ultimately contributing to the development of Type 2 diabetes. We sought to standardise and validate the intravenous glucose tolerance test (IVGTT), a commonly used technique to assess GSIS, in anaesthetised and conscious cannulated male Han Wistar rats. Methods: Male Han Wistar rats were cannulated via the right jugular vein and left carotid artery. Anaesthetised and chronically cannulated conscious models underwent IVGTT using increasing doses of glucose (0.2, 0.5 and 1.0 g glucose/kg LBM) or following pre-treatment with Exendin-4 (EX-4) before receiving a 0.5 g glucose/kg LBM bolus dose. Blood glucose, plasma insulin and plasma C-peptide were measured at time-points throughout the experiments. Results: Dose-dependent increases in blood glucose, insulin and C-peptide (where measured) were observed following administration of increasing doses of an intravenous glucose bolus in both the anaesthetised and conscious cannulated rats. The 0.5 g glucose/kg LBM bolus resulted in an intermediate response and was used in the second part of the study. EX-4 pre-treatment in combination with glucose resulted in GSIS potentiation, as assessed by plasma insulin measurement alone (anaesthetised model) or insulin and C-peptide measurements (conscious model). Discussion: The IVGTT was standardised in anaesthetised and conscious cannulated male Han Wistar rats by performing a glucose dose response study and validated by examining GSIS potentiation using EX-4. Based on these results, the 0.5 g glucose/kg LBM bolus dose is recommended as the dose to use to assess GSIS in any standardised screening phase of new compounds with the potential to enhance glucose-sensitive pancreatic function. The experimental conditions described in these studies could be transferred to disease models for more detailed assessment of novel compound efficacy. (c) 2008 Elsevier Inc. All rights reserved.