Extended Data Fig. 2: (related to Fig. 1). Transcriptional analysis of islets and sorted α and β cells reveals dysregulation of metabolic pathways in T2D β cells and immune signaling in T2D islets.

(a-c) Volcano plots illustrating differentially expressed genes between ND and T2D β cells (a; 352 genes), α cells (b; 248 genes), and islets (c; 565 genes) as obtained by DESeq2⁶⁴ (two-sided; multiple hypothesis corrected at FDR < 0.01). Lines denote cutoffs for fold-change (±1.5) and significance (FDR < 0.01); genes passing both thresholds are colored and select genes are labeled. (d-f) Enriched gene ontology terms (two-sided; multiple hypothesis corrected at FDR < 0.05) obtained from RNA-Enrich⁶⁶ were condensed using the RelSim function of Revigo (similarity = 0.5) and plotted in semantic space to emphasize relatedness. Dot size represents odds ratio and color represents p-value. Select terms are labeled. For α cells gene changes were most evident in amino acid and steroid signaling pathways and regulation of blood vessel morphology and for islets in cytokine signaling and other immune terms.