Despite the fact that high glucose levels, as well as the duration of hyperglycemia, are two major upstream regulators of β cell dedifferentiation, our experimental data has demonstrated that the increase in both CPHN cells and polyhormonal endocrine cells in the human IAPP-transgenic (HIP) rat (a model of T2D) is already present by 2–3 months of age, thereby preceding diabetes onset, elevations in glucose, or any measurable loss of β cell mass [89]. The gene discussed is IAPP; the disease is Hyperglycemia.