DYRK1A Inhibitors as Potential Therapeutics for β-Cell Regeneration for Diabetes

According to the World Health Organization (WHO), 422 million people are suffering from diabetes worldwide. Current diabetes therapies are focused on optimizing blood glucose control to prevent long-term diabetes complications. Unfortunately, current therapies have failed to achieve glycemic targets in the majority of people with diabetes. In this context, regeneration of functional insulin-producing human beta-cells in people with diabetes through the use of DYRK1A inhibitor drugs has recently received special attention. Several small molecule DYRK1A inhibitors have been identified that induce human beta-cell proliferation in vitro and in vivo. Furthermore, DYRK1A inhibitors have also been shown to synergize beta-cell proliferation with other classes of drugs, such as TGF beta inhibitors and GLP-1 receptor agonists. In this perspective, we review the status of DYRK1A as a therapeutic target for beta-cell proliferation and provide perspectives on technical and scientific challenges for future translational development.