RSPO1, A Potent Inducer of Pancreatic Beta Cell Neogenesis

The study identifies RSPO1 as a potent inducer of pancreatic β cell neogenesis, which could be a promising alternative therapy for diabetes. RSPO1 activates the Wnt/β-catenin pathway, significantly increasing β cell replication in vitro, ex vivo, and in vivo. In NOD mice, RSPO1 administration increases β cell mass, preventing hyperglycemia, and maintains normoglycemia in chemically induced diabetes models. RSPO1 treatment of transplanted human islets results in a 2.78-fold increase in functional human β cell numbers within 60 days. The study also highlights the necessity of RSPO1's interaction with Lgr4 and Znrf3 receptors and confirms the role of β-catenin in β cell proliferation. An engineered version of RSPO1 with an IgG FC domain extends its half-life, allowing weekly administration to prevent hyperglycemia in NOD mice. These findings suggest RSPO1's potential as a therapeutic strategy for diabetes by promoting β cell replication and function, although further research is needed to address limitations such as receptor binding data and bioavailability.