Biomedical importance of the ubiquitin-proteasome system in diabetes and metabolic transdifferentiation of pancreatic duct epithelial cells into β-cells.

The ubiquitin-proteasome system (UPS) is a major pathway for cellular protein degradation. The molecular function of the UPS is the removal of damaged proteins, and this function is applied in many biological processes, including inflammation, proliferation, and apoptosis. Accumulating evidence also suggests that the UPS also has a key role in pancreatic β-cell transdifferentiation in diabetes and can be targeted for treatment of diabetic diseases. In this review, we summarized the mechanistic roles of the UPS in the biochemical activities of pancreatic β-cells, including the role of the UPS in insulin synthesis and secretion, as well as β-cell degradation. Also, we discuss how the UPS mediates the transdifferentiation of pancreatic duct epithelial cells into β-cells as the experimental basis for the development of new strategies for the treatment of diabetes in regenerative medicine.