Fig. 1.

Molecular model underlying impaired PDX1 function in β cells under diabetes. Oxidative stress induced by chronic hyperglycemia upregulates JNK signaling in β cells. JNK impairs insulin signaling through the increase in IRS-1 serine phosphorylation and decrease in functioning tyrosine phosphorylation. Impaired Akt activity fails to phosphorylate FOXO1, leading to its nuclear localization. Nuclear-localized FOXO1 induces the nucleocytoplasmic translocation of PDX1, which eventually results in the deterioration of PDX1 function and β-cell function. IRS insulin receptor substrate