Dietary carbohydrates modulate islet transcriptome changes in response to high-fat diets. A: principle component analysis of islet whole genome array from mice exposed for 12 wk to either low-fat control (LF; n = 3), high-fat (HF; n = 2); high-fat, high-sugar (HFHS; n = 3); or high-fat ketogenic (HFKETO; n = 3) diets. PC1 indicates principle component 1 and PC2, principle component 2. B: analysis of differentially upregulated and downregulated genes in isolated islets of LF, HF, HFHS, and HFKETO mice. C and D: functional gene ontology (GO) enrichment analysis shows top 5 pathways significantly upregulated (or downregulated) in HF and HFHS or HFKETO vs. LF islets. E and F: gene-set enrichment analysis (GSEA) performed using preranked analysis of genes expressed in HF and HFKETO islets using genes annotated to either GO biological process “Cell Division” or GO biological process “Hormone Secretion.”