Molecular Mechanisms of Proglucagon Trafficking in Pancreatic Alpha Cells

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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.