Both PDX1 and HNF1A were downregulated in enriched beta cell fractions from type 2 diabetic OD, with PDX1 targeting ARG2. Downregulation of HNF1A, which lies upstream of PDX1, and upregulation of REST, point to de-differentiation of beta cells in type 2 diabetes. The gene discussed is REST; the disease is type 2 diabetes mellitus.