Refining mouse glucose homeostasis assessments

完善小鼠葡萄糖稳态评估

• 批准号: NC/X000923/1
• 负责人: Kate Ellacott
• 金额: $ 9.03万
• 依托单位: UNIVERSITY OF EXETER
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FX000923%2F1
• 关键词: Refining; mouse; glucose; homeostasis; assessments

Mice are often used in research into new treatments for diabetes. This project will improve the tests that we perform in mice used for diabetes research by making them more like those used in human medicine. The new method we propose will also improve animal welfare as the mice need less handling, which can be stressful for them. Diabetes is a common often life-long condition which occurs when the processes for controlling the amount of sugar (glucose) in our blood stop working properly. Glucose is an important fuel source for our body. Our bodies need to carefully control the amount of glucose in our blood so all our cells and organs have enough energy to work normally, but too much blood glucose can also be harmful. The process of balancing the amount of sugar in our blood is called glucose homeostasis and is controlled cooperatively by organs in our bodies communicating. This involves producing chemical messengers called hormones. Hormones are produced in one type of organ, such as the liver, and the information is received by another organ, such as the brain, which responds appropriately. Because diabetes is so common and has serious health consequences, we need to do more research to understand what causes it and how we can treat it. There are already some diabetes treatments available, such as giving the hormone insulin, but sometimes these treatments have bad side effects or don't work well in some groups of people. Because diabetes is a disease of the whole body, we need to study it in living animals to truly understand it. Mice are often used for this as they have the same hormones and processes for regulating their blood glucose as people, and have been used for research in this area for over fifty-years.When doctors think a person might have diabetes, they often perform a test called a glucose tolerance test. In this test a person drinks a very sweet drink containing lots of sugar, to rapidly increase their blood glucose levels. After a period of time, they then have a blood test to measure how much glucose is still in their blood. During this test, if a person's blood glucose regulatory systems are working properly, their body activates processes to bring their blood glucose levels down. If these are not working properly, their blood glucose levels will remain higher for longer; this indicates that they might have or be at risk of developing diabetes. A very similar glucose tolerance test is also used in mice during diabetes research, except that their blood glucose levels are increased by giving them an injection or by using a tube to put the glucose straight into their stomachs. While these approaches are effective, they are not ideal for two reasons. Firstly, unlike when this test is done in people, the glucose does not pass through the mouth of the mice. Because we know that the mouth is an important, yet underappreciated, first stage step in glucose sensing by the body this means that the test in the mouse is not completely comparable to the human test. Secondly, both methods of giving glucose involve picking the mouse up, which can be stressful. We always want to minimise stress in mice for their welfare, but also because it can change their blood glucose levels which can impact the test results. This project will test a new method of giving mice glucose during the glucose tolerance test, which is adapted from a technique established by a group of scientists in Europe. Because mice like sweet things, you can train them to voluntarily drink glucose from a small tube when offered. This already works for giving drugs to mice in research studies and we want to adapt it for use in glucose tolerance testing. Once we achieve this, we will compare this new method with the old approaches to confirm that it is as effective and less stressful for the mice. We have already talked to other leading scientists across the world, and they are excited to work with us and to start using this new approach.

老鼠经常被用于研究糖尿病的新疗法。该项目将改进我们在用于糖尿病研究的小鼠中进行的测试，使其更像用于人类医学的测试。我们提出的新方法也将改善动物福利，因为小鼠需要更少的处理，这对它们来说可能是压力。糖尿病是一种常见的终身疾病，发生在控制血液中糖（葡萄糖）量的过程停止正常工作时。葡萄糖是我们身体的重要燃料来源。我们的身体需要仔细控制血液中的葡萄糖含量，这样我们所有的细胞和器官都有足够的能量来正常工作，但过多的血糖也可能是有害的。平衡我们血液中糖的量的过程被称为葡萄糖稳态，并通过我们身体中的器官进行协调控制。这涉及到产生一种叫做激素的化学信使。激素是在一种器官中产生的，如肝脏，信息被另一种器官接收，如大脑，它会做出适当的反应。由于糖尿病是如此常见，并有严重的健康后果，我们需要做更多的研究，以了解它的原因和我们如何治疗它。已经有一些糖尿病治疗方法，如给予激素胰岛素，但有时这些治疗有不良的副作用或在某些人群中效果不佳。因为糖尿病是一种全身性疾病，我们需要在活体动物身上进行研究才能真正了解它。老鼠经常被用于这一领域，因为它们具有与人类相同的激素和调节血糖的过程，并且已经被用于这一领域的研究超过50年。当医生认为一个人可能患有糖尿病时，他们通常会进行一项称为葡萄糖耐量试验的测试。在这个测试中，一个人喝了一种含有大量糖的非常甜的饮料，以迅速增加他们的血糖水平。一段时间后，他们会进行血液测试，以测量血液中仍有多少葡萄糖。在这项测试中，如果一个人的血糖调节系统正常工作，他们的身体会激活过程，使他们的血糖水平下降。如果这些不能正常工作，他们的血糖水平将保持更长时间;这表明他们可能患有糖尿病或有患糖尿病的风险。在糖尿病研究中，一种非常类似的葡萄糖耐量试验也用于小鼠，除了通过注射或使用试管将葡萄糖直接放入胃中来增加血糖水平。虽然这些方法是有效的，但由于两个原因，它们并不理想。首先，与在人体中进行的测试不同，葡萄糖不会通过小鼠的口腔。因为我们知道嘴是身体葡萄糖感知的重要但未得到充分重视的第一阶段，这意味着小鼠测试与人体测试不完全可比。其次，这两种给予葡萄糖的方法都涉及到将老鼠捡起来，这可能会带来压力。我们总是希望尽量减少小鼠的压力，以确保它们的福利，但也因为它可以改变它们的血糖水平，从而影响测试结果。该项目将测试一种在葡萄糖耐量试验期间给小鼠葡萄糖的新方法，该方法改编自欧洲一组科学家建立的技术。因为老鼠喜欢甜的东西，你可以训练它们在提供葡萄糖时自愿从一个小管中喝葡萄糖。这已经适用于在研究中给小鼠药物，我们希望将其用于葡萄糖耐量测试。一旦我们实现了这一点，我们将把这种新方法与旧方法进行比较，以确认它对小鼠同样有效，压力更小。我们已经与世界各地的其他领先科学家进行了交谈，他们很高兴与我们合作并开始使用这种新方法。