Regeneration of Pancreatic beta-Cells for Diabetes Therapeutics by Natural DYRK1A Inhibitors

The pathogenesis of diabetes mellitus is characterized by insulin resistance and islet beta-cell dysfunction. Up to now, the focus of diabetes treatment has been to control blood glucose to prevent diabetic complications. There is an urgent need to develop a therapeutic approach to restore the mass and function of beta-cells. Although exogenous islet cell transplantation has been used to help patients control blood glucose, it is costly and has very narrow application scenario. So far, small molecules have been reported to stimulate beta-cell proliferation and expand beta-cell mass, increasing insulin secretion. Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) inhibitors can induce human beta-cell proliferation in vitro and in vivo, and show great potential in the field of diabetes therapeutics. From this perspective, we elaborated on the mechanism by which DYRK1A inhibitors regulate the proliferation of pancreatic beta-cells, and summarized several effective natural DYRK1A inhibitors, hoping to provide clues for subsequent structural optimization and drug development in the future.