Project 454361

Insulin is secreted from cells of the pancreatic islets of Langerhans into the blood after a meal to control blood sugar levels. In type 1 diabetes (T1D) islet cells are destroyed by an auto-immune reaction. In type 2 diabetes (T2D), islet cells fail to produce enough insulin to meet the body's needs. Thus, understanding the factors that control insulin production by islet cells is an important step towards determining the causes of diabetes, the potential for diabetes reversal, an ultimately prevention of the disease. Even in people without diabetes insulin levels in the blood are extremely variable and is impacted by factors that include nutrition, genetics, and exposure to environmental chemicals. This variation can also be seen in insulin secreted by pancreatic islets isolated from the pancreas of organ donors. Led by the Alberta Diabetes Institute IsletCore, one of the world's top pancreas tissue biobanks, our team of experts will catalog the variability in human insulin secretion, islet cell functions, and molecular profiles across many pancreas organ donors with and without diabetes. The result will be a comprehensive 'encyclopedia' and web portal that links genetics, gene expression, environmental chemical exposures, metabolites, islet proteins, and more with detailed cellular functions of insulin-producing islet cells. Our Team will also answer key questions about how genetic-risk for diabetes acts to impair insulin secretion; about personalized insulin responses to different nutrients; and about the links between environmental pollution and reductions in insulin secretion. We will also make this 'encyclopedia' available to researchers around the world, supporting a better understanding of human insulin secretion and diabetes.