The decrease in insulin/Igf signaling affects not only Foxo1, but also Gsk-3β function, and as evidenced by Tanabe et al., Gsk-3β controls β-cell mass in insulin-resistant diabetic models where the loss of one allele of Gsk-3β preserved β-cell mass and prevented diabetes in Irs2−/− mice. Here, INS is linked to diabetes mellitus.