Understanding the hepatic microenvironment to improve function and survival of transplanted pancreatic islets in diabetes

1型糖尿病（T1DM）患者一生中注射6.5万次胰岛素，检查血糖8万次。T1DM是由人体自身防御细胞破坏β细胞引起的。β细胞是朗格汉斯胰岛中专门产生胰岛素的细胞，朗格汉斯胰岛是分散在胰腺中产生激素的部分。胰岛素是一种控制血糖水平的信号分子。这种破坏会阻止胰腺中的β细胞产生胰岛素，这意味着血糖水平会上升到无法控制的程度。因此，患者需要全天定期注射胰岛素来控制血糖水平。这影响了英国大约40万人，其中2.9万是儿童，预计到2035年将增加到60万，4.8万。全世界这个数字大约是3700万。这对医疗保健系统来说是一个重大的财政负担，在2010/11年度，NHS在T1DM患者的直接护理上花费了10亿英镑。严重的T1DM可导致视力丧失、肾衰竭、中风和心脏病，导致衰弱的健康问题，甚至在年轻时死亡。胰岛移植提供了一条途径，通过替换已被破坏的胰岛细胞来帮助这些患者改善血糖控制。它可以让患者在不注射的情况下再次产生胰岛素。它包括从器官捐献者的胰腺中取出胰岛细胞，分离出产生胰岛素的胰岛细胞，然后通过输注将它们添加到肝脏中。胰岛移植对一些病人效果很好，但并不完美。它可以防止患者血糖控制不佳达到危险水平，但许多患者即使在胰岛移植后仍需要额外注射胰岛素，有些移植只会在短时间内起作用。大多数患者还需要进行不止一个胰岛移植，这意味着很少有患者能从这种治疗中受益，因为器官捐赠者的数量非常有限。许多胰岛细胞在移植后不能在肝脏中存活。我们将研究为什么会发生这种情况，以及如何改进这种情况，以便胰岛移植可以更好，更长时间，为更多的人服务。我们将在实验室中仔细观察正常胰腺样本中的胰岛细胞，这样我就可以确定它们从其他邻近细胞那里获得的支持，从而鼓励它们在正常环境中良好地工作。然后，我们将把我们的发现与胰岛细胞输注样本进行比较。这将使我们看到在胰岛与邻近细胞和胰腺的其余部分分离后，存在哪些支持细胞和途径。然后，我们还将比较胰岛细胞被放入肝脏后的环境，以及邻近的肝细胞如何影响胰岛细胞的存活和功能。我们希望找到方法，在胰岛细胞与胰腺分离后和移植后为胰岛细胞创造一个更有利的环境，使更多的细胞存活并更有效地产生胰岛素。回答这些问题将使更多的人可以接受胰岛移植，因为不需要重复移植。因此，更多患有严重T1DM并发症的患者可以从这种治疗中受益。请点击我的视频链接，观看我研究的视觉总结。https://youtu.be/bWfo4JknIx8

A patient with Type 1 Diabetes Mellitus (T1DM) administers 65,000 insulin injections and checks their blood sugar 80,000 times during their lifetime. T1DM results from destruction of beta-cells by the body's own defensive cells. Beta-cells are specialist insulin producing cells in the Islets of Langerhans which are hormone producing sections scattered within the pancreas. Insulin is a signalling molecule which controls blood sugar levels. This destruction, prevents the beta-cells in the pancreas from producing insulin, meaning that blood sugar levels will rise out of control. As a result, patient's need to inject insulin regularly, throughout the day, to control their sugar levels. This affects approximately 400,000 people in the UK, 29,000 of whom are children with a predicted rise to 600,000 and 48,000 in 2035. Worldwide this figure is approximately 37 million. This represents a significant financial burden for the healthcare system and in 2010/11 the NHS spent £1 billion on direct patient care for T1DM. Severe T1DM can cause loss of vision, kidney failure, strokes and heart disease causing debilitating health problems and death at a young age.Islet transplantation offers an avenue to help these patients improve their sugar control by replacing the islet cells which have been destroyed. It allows patients to produce insulin again without injections. It involves taking islet cells from the pancreas of an organ donor and separating the insulin producing islet cells out, before adding them to the liver through an infusion. Islet transplant works well for some patients, but it is not perfect. It can stop patients from having dangerous levels of poor sugar control, but many patients will continue to need additional insulin injections even after islet transplant and some transplants will only work for a short period of time. Most patients will also need to have more than one islet transplant, meaning that less patients can benefit from this treatment as the number of organ donors is very limited. Many of the islet cells do not survive in the liver after transplant. We will investigate why this happens and how this can be improved, so that islet transplants can work better, for longer, for more people.We will look closely at islet cells in normal pancreas samples in the laboratory so I can establish the support they receive from other neighbouring cells which encourage them to work well in their normal environment. We will then compare what we discover to samples of islet cell infusions. This will allow us to see what supporting cells and pathways are present after the islets have been separated from their neighbouring cells and the rest of the pancreas. We will then also compare the islet cell environment after they have been placed into the liver and how the neighbouring liver cells influence islet cell survival and function. We hope to find ways to create a more supportive environment for islet cells after separation from the pancreas and after transplant, so that more cells survive and produce insulin more effectively. Answering these questions will make islet transplant available for more people as repeat transplants will not be required. Therefore, more patients suffering from the complications of severe T1DM can benefit from this treatment.Please follow the link to my video for a visual summary of my research.https://youtu.be/bWfo4JknIx8