In summary, our data and a study from Zheng et al., which showed that p53-deficient mice were more susceptible to STZ-induced diabetes (Zheng et al., 2005), suggest that the flow of the STZ-mediated β-cell failure is as follows: (i) low-dose STZ administration induces modest DNA damage, (ii) modest DNA damage does not kill cells but activates p53, (iii) activated p53 induces a series of p53-dependent genes, (iv) p53-induced factors arrest β-cell proliferation, and (v) STZ-induced stress turns off a wide range of genes that are essential for β-cell functions. The gene discussed is TP53; the disease is diabetes mellitus.