NKX6-1 and Hyperglycemia: As shown in mouse models of diabetes and rats after near total pancreatectomy, hyperglycemia leads to significant β-cell degranulation, a reduction in insulin content, decreased expression of mature β-cell markers (Pdx1, Nkx6.1, and MafA), and elevated expression of progenitor cell markers, such as Ngn3, Nanog, and L-Myc [30,45,46,47].