Table 1.

Overview and comparison of the islet’s physiological, transcriptional, and epigenetic response to dietary interventions.

Dietary Interventions	Islet Phenotype	Transcriptional Adaptations	Epigenetic Adaptations	References
High fat diet/High fat + high sugar diet	Increased basal insulin and glucagon secretion Decreased β-cell and α-cell function Increased β-cell proliferation and mass Increased β-cell apoptosis	Rapid increase in cell cycle and proliferation transcripts Decreased β-cell identity, oxidative metabolism, insulin secretion, and exocytosis transcripts Increased immaturity (dedifferentiation), glycolytic, ER stress, and inflammatory transcripts Increased transcriptional entropy Similar transcriptional signature (by PCA) between HF and HFHS	Increased bivalency of Polycomb regulated promoters and enhancers Increased H3K27ac at loci regulating glycolytic and proliferative gene networks miRNA and lncRNA mediated increase in cell cycle and decrease of β-cell identity transcripts	(31–38)
High sugar diet	Increased basal glucagon secretion Reduced β-cell and α-cell function Reduced β-cell mass	Unknown	Unknown	(39–41)
Ketogenic diet	No change in basal insulin secretion No change in β-cell function No change in β-cell proliferation, mass, or apoptosis	Decreased cell cycle, ER stress, and inflammatory transcripts Increased insulin secretion and exocytosis transcripts Similar transcriptional signature (by PCA) between ketogenic and control islet	miRNA mediated decrease in cell cycle and increase in mitochondrial metabolism transcripts	(32, 42, 43)
Low protein/BCAA diet	Reduced basal insulin secretion No change in β-cell function	Unknown	Unknown	(44–46)
Time-restricted feeding	Reduced basal insulin secretion Increased circadian β-cell function No change in β-cell proliferation and mass	Increased protein/insulin processing, insulin secretion, kinase signalling and metabolic transcripts during feeding Increased lipid metabolism, inflammatory, and nutrient sensing transcripts during fasting Maintenance of core circadian clock transcripts and overall circadian rhythm in gene expression	Increased H3K27ac during feeding Maintenance of circadian rhythmicity in chromatin accessibility LSD1 recruitment and H3K4me1 demethylation of feeding activated loci Increased DBP activity at H3K27ac marked insulin secretory loci	(47, 48)
Alternate day fasting	Reduced basal insulin secretion Increased β-cell function Reduced β-cell apoptosis	Reduced p53 and IL-6 activity Increased p62 activity during fasting	Unknown	(49, 50)
Prolonged fasting	Increased β-cell proliferation and regeneration Reduced β-cell apoptosis	Increased β-cell identity and immaturity transcripts	Unknown	(51)