Approximately 1 in 11 people worldwide is afflicted by diabetes, a disease caused by a shortage of beta cells. The current standard of care for patients with severe diabetes is insulin therapy or pancreatic islet transplantation. However, insulin therapy requires frequent insulin injection, detailed dose calibration and close monitoring of blood glucose; for islet transplantation, there is a global shortage of organ donors and the procedure requires lifelong immunosuppression. As an alternative way to treat diabetes, beta cell regeneration methods have been explored with the aim to compensate for the underlying beta cell deficiency of the disease.

Human beta cells possess the potential to regenerate during normal cell turnover and under various physiological stresses. Therefore, to promote beta cell proliferation, one of the powerful approaches is to exploit the endogenous machinery of beta cell replication. However, research on human beta cell regeneration is hampered by the facts that in adult human, the basal rate of beta cell replication is less than 0.1% and bulk assays do not have enough sensitivity to distinguish signals from these rare proliferation events. To address this problem, we will develop and implement an experimental system to achieve targeted isolation of proliferating beta cells from primary human pancreas and characterize their global gene expression program.

Our work will help to identify novel pathways to increase beta cell mass both in the islet transplantation context and directly in patients with diabetes who have residual beta cells.