Endoplasmic reticulum stress and forkhead box protein O1 inhibition mediate palmitic acid and high glucose-induced β-cell dedifferentiation

Figure 5 High glucose and palmitic acid induced β-cell dedifferentiation due to endoplasmic reticulum stress. A and B: Electron micrograph (A) and statistical analysis (B) of the endoplasmic reticulum lumen width in INS-1 cell treated with bovine serum albumin (BSA) (control), 25 mmol/L glucose plus 300 μmol/L palmitic acid (Glu + PA), or 25 mmol/L glucose plus 300 μmol/L palmitic acid plus 1 μmol/L AS1842856 (Glu + PA + AS) for 36 hours; C and D: Western blot (C) and quantification (D) of aldehyde dehydrogenase 1 family member A3 (Aldh1a3), pancreatic and duodenal homeobox 1, and p-Eif2α levels in INS-1 cell treated with BSA (control), Glu + PA, 300 μmol/L 4-phenyl butyric acid (4-PBA), or Glu + PA + 4-PBA for 36 hours; E and F: INS-1 cell treated with 5 μg/mL tunicamycin for 12 hours, and western blot (E) and quantification (F) of Aldh1a3 and p-Eif2α levels. Data are presented as means ± SEM. ^aP < 0.05. ^bP < 0.01. ^cP < 0.001. ^dP < 0.0001. Glu: Glucose; PA: Palmitic acid; AS: AS1842856; Pdx1: Pancreatic and duodenal homeobox 1; Aldh1a3: Aldehyde dehydrogenase 1 family member A3; ER: Endoplasmic reticulum; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; 4-PBA: 4-phenyl butyric acid.