Molecular Mechanisms of Proglucagon Trafficking in Pancreatic Alpha Cells

胰腺α细胞中胰高血糖素原运输的分子机制

• 批准号: RGPIN-2022-04691
• 负责人: Dhanvantari, Savita
• 金额: $ 2.04万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=760710
• 关键词: Molecular; Mechanisms; Proglucagon; Trafficking; Pancreatic

Background: Cells from organs that secrete hormones are called endocrine cells. Hormones are vital in regulating physiological processes in the body, such as sugar and fat metabolism. We wish to study the cellular mechanisms of how endocrine cells secrete hormones. Our research focusses on a hormone called glucagon, which is secreted from endocrine alpha cells in the pancreas to maintain blood sugar levels. Inside the alpha cell, glucagon is contained in tiny specialized packages called granules. Our past work has shown that these granules contain important molecules that affect how glucagon is secreted. We know that these granules have to be in particular locations within the cell in order for glucagon to be secreted in response to nutrients, but we don't know how they get to these locations. This is an important question because it will provide clues on how glucagon secretion is controlled and will broaden our understanding of how nutrients, such as sugars, fats and proteins, are regulated in the body. Our question: How does the location of granules inside the alpha cells of the pancreas affect the secretion of glucagon? Our methodology: Granules that contain glucagon may interact with other structures in the cell to get to their proper place for secretion. We will identify these structures and show how they control granule movement to regulate the secretion of glucagon. 2) We will use state-of-the-art technologies in advanced microscopy to identify new networks of proteins that direct the movement of granules inside the alpha cell. Expected Results and Significance: We expect to discover new ways in which granules within the alpha cells are transported to their proper locations for the secretion of glucagon from the pancreas. These results will explain why endocrine cells are important in regulating the metabolism of nutrients in the body. Who will this research benefit? 1) The research fields of nutrient metabolism and diabetes. When we understand the ways in which the alpha cell controls the secretion of glucagon, it will help us to explain nutrient metabolism in both health and disease. 2) The people who train in my lab. Both undergraduate and graduate students will gain experience in designing and conducting experiments, technical expertise in advanced microscopy, skills in organization and teamwork and how to build a welcoming and inclusive workspace. 3) Canada will also benefit from both a research and training perspective. Our talented students will be employable in government, educational and research institutes, and industry, and they may also create their own companies or organizations.

背景：来自分泌激素的器官的细胞称为内分泌细胞。激素在调节体内的生理过程中至关重要，如糖和脂肪代谢。我们希望研究内分泌细胞如何分泌激素的细胞机制。我们的研究集中在一种叫做胰高血糖素的激素上，它是由胰腺内分泌α细胞分泌的，用于维持血糖水平。在α细胞内，胰高血糖素包含在称为颗粒的微小专门包装中。我们过去的工作表明，这些颗粒含有影响胰高血糖素分泌的重要分子。我们知道这些颗粒必须位于细胞内的特定位置，以便胰高血糖素响应营养素分泌，但我们不知道它们如何到达这些位置。这是一个重要的问题，因为它将提供有关胰高血糖素分泌如何控制的线索，并将扩大我们对糖，脂肪和蛋白质等营养物质在体内如何调节的理解。我们的问题是：胰腺α细胞内颗粒的位置如何影响胰高血糖素的分泌？我们的方法：含有胰高血糖素的颗粒可能与细胞中的其他结构相互作用，以到达其适当的位置进行分泌。我们将确定这些结构，并显示它们如何控制颗粒运动来调节胰高血糖素的分泌。2)我们将在先进显微镜中使用最先进的技术来识别指导α细胞内颗粒运动的新蛋白质网络。 预期结果及意义：我们期望发现新的方法，其中α细胞内的颗粒被运送到胰腺分泌胰高血糖素的适当位置。这些结果将解释为什么内分泌细胞在调节体内营养物质代谢方面很重要。 这项研究将使谁受益？1)营养代谢与糖尿病研究领域。当我们了解α细胞控制胰高血糖素分泌的方式时，它将有助于我们解释健康和疾病中的营养代谢。2)在我实验室训练的人。本科生和研究生都将获得设计和进行实验的经验，先进显微镜的技术专长，组织和团队合作技能以及如何建立一个热情和包容的工作空间。3)加拿大也将从研究和培训的角度受益。我们有才华的学生将在政府，教育和研究机构，以及行业就业，他们也可以创建自己的公司或组织。