(A) Volcano plot identifying differentially expressed genes (FC > 1.2; FDR < 0.05) from RNA-Seq performed on islets of β-Slc4a4+/+ (Slc4a4fl/fl+/+) and β-Slc4a4–/– (Slc4a4fl/flIns2Cre/+) mice exposed to 8 weeks of an HFD (n = 3 independent samples per genotype). (B) Network analysis illustrating the interaction between significantly enriched (P < 0.05) KEGG pathways of differentially expressed genes identified in β-Slc4a4+/+ (Slc4a4fl/fl+/+) (top) and β-Slc4a4–/– (Slc4a4fl/flIns2Cre/+) (bottom) HFD islets. Key pathways associated with β cell function, identity, and stress are highlighted. (C) Gene set enrichment analysis of islet transcriptome in β-Slc4a4+/+ (Slc4a4fl/fl+/+) and β-Slc4a4–/– (Slc4a4fl/flIns2Cre/+) HFD islets for β cell identity (KEGG – maturity onset of diabetes in the young pathway; P < 0.001) (D) Heatmap visualization of transcriptional changes of genes encoding β cell identity and dedifferentiation in β-Slc4a4+/+ (Slc4a4fl/fl+/+) and β-Slc4a4–/– (Slc4a4fl/flIns2Cre/+) HFD islets. (E) Representative examples of islets immunostained for insulin (red), Nkx6.1 (white), Aldh1a3 (green), and DAPI (blue) imaged at 20× obtained from β-Slc4a4+/+ (Slc4a4fl/fl+/+) and β-Slc4a4–/– (Slc4a4fl/flIns2Cre/+) mice exposed to 8 weeks of an HFD. Scale bars: 20 μm in all images. Images are representative of n = 3 mice per group.