PURPOSE OF REVIEW: Therapies that increase functional β-cell mass may be the best long-term treatment for diabetes. Significant resources are devoted toward this goal, and progress is occurring at a rapid pace. Here, we summarize recent advances relevant to human β-cell regeneration.

RECENT FINDINGS: New β-cells arise from proliferation of pre-existing β-cells or transdifferentiation from other cell types. In addition, dedifferentiated β-cells may populate islets in diabetes, possibly representing a pool of cells that could redifferentiate into functional β-cells. Advances in finding strategies to drive β-cell proliferation include new insight into proproliferative factors, both circulating and local, and elements intrinsic to the β-cell, such as cell cycle machinery and regulation of gene expression through epigenetic modification and noncoding RNAs. Controversy continues in the arena of generation of β-cells by transdifferentiation from exocrine, ductal, and alpha cells, with studies producing both supporting and opposing data. Progress has been made in redifferentiation of β-cells that have lost expression of β-cell markers.

SUMMARY: Although significant progress has been made, and promising avenues exist, more work is needed to achieve the goal of β-cell regeneration as a treatment for diabetes.