UC Davis

Pancreatic islets contain several types of hormone-expressing cells to help regulate glucose homeostasis. Chief among these is beta cells which secrete insulin to lower blood glucose levels. Diabetes, which currently impacts over 37 million Americans, ensues when beta cells are destroyed by the body’s own immune system or when they become dysfunctional caused by a myriad of genetic and environmental factors. Consequently, the major question becomes how best to replace the lost and impaired beta cells. To this end, we discovered a novel population of immature virgin beta cells which may potentially serve as a new source to generate functionally mature beta cells as a therapeutic treatment for diabetes.

In this dissertation, we further characterized virgin beta cells to learn more about their unique properties that make them distinct from other known beta cell subpopulations. Using various transgenic mice, complex lineage-tracing techniques, and immunohistochemical analyses, we determined several novel insights about virgin beta cells. Chapter 1 reviews the discovery of virgin beta cells and the many unanswered questions remaining about them. Chapter 2 examined the proliferation capacity and maturation potential of virgin beta cells. Chapter 3 elucidated the role of pancreatic alpha and delta cells in the formation and maintenance of virgin beta cells. Chapter 4 interrogated the contribution of artemether, an anti-malarial drug, in the generation of new beta cells via beta cell transdifferentiation from alpha cells. Lastly, Chapter 5 summarizes all the original, including unpublished, work performed in this dissertation, concluding remarks, and various exciting direction for future studies.