Role of Pancreatic Delta Cells and Somatostatin in Glucose Homeostasis

Blood glucose homeostasis is the maintenance of blood glucose levels within a narrow range. The tight regulation of blood glucose levels is critical, as hypoglycemia can be acutely fatal and hyperglycemia leads to diabetes and its associated complications. Pancreatic islets play an essential role in maintaining normoglycemia. They are composed of insulin-secreting beta cells, glucagon-secreting alpha cells, and somatostatin-secreting delta cells, which coordinate to regulate blood glucose levels through paracrine interactions. Breakdown of these interactions contributes to the development of diabetes.This dissertation focuses on how beta, alpha, and delta cells are affected by changes in paracrine interactions and disease, with a focus on how delta cells contribute to the regulation of beta cells as well as alpha cells. Chapter 1 provides an overview of the beta, alpha and delta cells within the pancreatic islet and how their interactions shape glucose homeostasis, as well as a section on other known somatostatin-secreting cells. Chapter 2 focuses on UCN3 and its role as a marker but not a driver of beta cell maturity. Chapter 3 investigates how SST signaling affects gene expression in beta and alpha cells. Chapter 4 presents work on the contribution of delta cells and SST signaling to the glycemic set point and how this occurs through paracrine interaction with beta cells. Chapter 5 further discusses the role of delta cells in the control of blood glucose levels. Chapter 6 returns to the topic of beta cell and alpha cell gene expression and what changes occur in a model of obesity. Chapter 7 provides a summary of the work and potential future directions