Figure 2.

Oxidative stress compromises beta cell identity by altering expression of beta cell maturity genes and beta cell disallowed genes. Loss of beta cell identity through de-/trans-differentiation processes contributes to beta cell failure in diabetic condition. Oxidative stress-reduced expression of beta cell-fate markers such as duodenal homeobox factor-1 (Pdx-1), musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), paired box 4 (Pax4) and homeobox protein Nkx6.1, decreases the expression of insulin (Ins) and glucose transporter GLUT1 and promotes the expression of progenitor markers such as SRY-box transcription factor 9 (SOX9) and hairy and enhancer of split-1 (HES1), suggesting occurrence of dedifferentiation process. By reducing expression of Pdx-1, oxidative stress may also lead to overexpression of alpha cell specific aristaless-related homeobox gene factor (Arx) and consequently to transdifferentiation of beta cells into alpha cells.