Project 446708

Insulin is the primary hormone responsible for controlling blood sugar levels. It is produced by the pancreatic islets of Langerhans, rises after a meal to promote energy storage, and falls during fasting to allow energy mobilization. The levels of insulin in the blood vary tremendously amongst people. Nutrition, age, sex, genetics, and environmental exposures are all important factors likely to impact insulin levels. However, the underlying mechanisms by which these factors effect islet insulin production at the cellular level - are not clear. This is important since altered insulin secretion from islets contributes to obesity, metabolic syndrome, and essentially all forms of diabetes. For example the failure to maintain insulin production in the face of insulin resistance determines the onset of type 2 diabetes (T2D), while the autoimmune destruction of islet cells underlies type 1 diabetes (T1D). Our Team seeks to understand the variability in human islet function in relation to genetic and environmental impacts on diabetes risk, and to identify mechanisms of islet dysfunction in diabetes. To do this we will take advantage of extensive data on the molecular, cellular, and physiological function of islets from human organ donors. We will also produce tools and resources so that other researchers can explore this data to answer their own questions about islet dysfunction in diabetes.