Studies have suggested that elevated blood glucose levels and increased beta cell proliferation were a compensatory response against insulin resistance in 4-week-old db/db mice15, and that nuclear exclusion of Forkhead box protein O1 (FoxO1), a key downstream mediator of glucose or insulin signaling, was a contributing factor in beta cell proliferation in 4-week-old db/db mice15,19,20. Here, INS is linked to Insulin resistance.