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

Figure 4 Analysis of differentially expressed genes is associated with forkhead box O1-inhibition reinforced β-cell dedifferentiation. A: Heatmap of differential genes with a consistent expression trend in high glucose plus palmitate acid (Glu + PA) or high glucose plus palmitate acid plus AS1842856 (Glu + PA + AS), including 187 upregulated genes and 359 downregulated genes. Z-score indicators are shown on the right of the map; B: Kyoto Encyclopedia of Genes and Genomes enrichment pathway of differentially expressed genes (DEGs) in (A); C: Heatmaps of the top three enrichment pathways, including metabolic pathway, mitogen-activated protein kinase pathway and phosphatidylinositol 3-kinase-protein kinase B pathway; D: Top 20 hub genes from the protein-protein interaction network of DEGs. Different scores of the hub genes are shown as gradual colors (yellow indicates low scores, red indicates high scores); E: Verification of quantitative real-time polymerase chain reaction in endoplasmic reticulum stress-related genes. Glu: Glucose; PA: Palmitic acid; AS: AS1842856; MAPK: Mitogen-activated protein kinase; PI3K: Phosphatidylinositol 3-kinase; FC: Fold change; CTL: Cytotoxic T lymphocyte; KEGG: Kyoto Encyclopedia of Genes and Genomes; cAMP: Cyclic adenosine monophosphate; DEGs: Differentially expressed genes; NOD: Nucleotide-binding and oligomerization domain; FPKM: Fragments per kilobase of transcript per million mapped reads.