Arenarine D Promotes Pancreatic β Cell Proliferation Via DYRK1A Inhibition for T1DM Therapy.

Diabetes is a complex and refractory metabolic disease severely threatening human health. A common feature of both type 1 and advanced type 2 diabetes is the failure and loss of functional β-cells. Stimulating pancreatic β cell proliferation for endogenous regeneration represents the most direct therapeutic approach.Through screening of secondary metabolites from the endophytic fungus of Ajuga decumbens Thunb using a zebrafish model, we identified Arenarine D promoting β cell regeneration. In a low-dose STZ-induced T1DM mouse model, Arenarine D treatment lowered blood glucose and improved insulin resistance. Importantly, we found it promotes mouse β cell proliferation by inhibiting DYRK1A. To our knowledge, we are the first to report that Arenarine D can promote the proliferation of pancreatic β cells by inhibiting DYRK1A, and this effect stems from the replication of existing β cells rather than other pathways. This demonstrates the great potential of Arenarine D in the treatment of T1DM.