Characterization of human islet cells: functional and transcriptional studies

人类胰岛细胞的表征：功能和转录研究

• 批准号: G0801995/1
• 负责人: Olof Rorsman
• 金额: $ 75.17万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0801995%2F1
• 关键词: Characterization; human; islet; cells; functional

Pancreatic islets play a central role in plasma glucose regulation. They do so by secreting several hormones with key role in glucose homeostasis. In addition, the islet delta-cells secrete somatostatin, a peptide hormone that inhibits both insulin and glucagon release. Type-2 diabetes involves disturbances of both insulin and glucagon release. Studies on rodent islets have revealed the fundamental principles about how changes in plasma glucose levels stimulate or inhibit pancreatic islet hormone secretion. It is generally assumed ? without much justification - that data emanating from rodent studies can be extrapolated to man. The Human Islet Transplantation Centre in Oxford is one of two islet isolation centres in the UK. Via this centre we now have regular supply of high-quality human pancreatic islets. Over the last two years, we have characterized the electrophysiological and secretory characteristics of human beta-cells. We have found that human beta-cells differ from mouse beta-cells in a number of important ways. Collectively, the data obtained so far indicate that it is not possible to extrapolate rodent data to the situation in man. In order to understand the hormone secretion defects that associate with type-2 diabetes in man (rodent diabetes is a rare clinical disorder!), we require a much more detailed picture of the functional characteristics of human islet cells. This information should be highly relevant in the ongoing efforts developing new antidiabetic medicines.

胰岛在血糖调节中起核心作用。它们通过分泌几种在葡萄糖体内平衡中起关键作用的激素来实现这一点。此外，胰岛δ细胞分泌生长抑素，一种抑制胰岛素和胰高血糖素释放的肽激素。2型糖尿病涉及胰岛素和胰高血糖素释放的紊乱。对啮齿动物胰岛的研究揭示了血糖水平变化如何刺激或抑制胰岛激素分泌的基本原理。一般认为？没有太多的理由-来自啮齿动物研究的数据可以外推到人类身上。牛津的人类胰岛移植中心是英国两个胰岛分离中心之一。通过这个中心，我们现在可以定期供应高质量的人类胰岛。在过去的两年中，我们已经表征了人类β细胞的电生理和分泌特性。我们已经发现，人类β细胞在许多重要方面不同于小鼠β细胞。总的来说，迄今为止获得的数据表明，不可能将啮齿动物的数据外推到人类的情况。为了了解与人类2型糖尿病相关的激素分泌缺陷（啮齿动物糖尿病是一种罕见的临床疾病！），我们需要对人类胰岛细胞的功能特征有更详细的了解。这一信息应该是高度相关的正在进行的努力，开发新的抗糖尿病药物。