Temporal metabolic and transcriptomic characteristics crossing islets and liver reveal dynamic pathophysiology in diet-induced diabetes

Summary To investigate the molecular mechanisms underlying islet dysfunction and insulin resistance in diet-induced diabetes, we conducted temporal RNA sequencing of tissues responsible for secretion (islets) action (liver) every 4 weeks mice on high-fat (HFD) or chow diet 24 weeks, linking to longitudinal profile metabolic characteristics. The diverse responses α, β, δ cells glucose palmitate indicated HFD-induced dynamic deterioration function from dysregulation failure. Insulin developed with variable time course different tissues. Weighted gene co-expression network analysis Ingenuity Pathway Analysis implicated islets liver jointly programmed β-cell compensatory adaption via cell proliferation at early phase irreversible by inappropriate immune response later stage, identified interconnected molecules including growth differentiation factor 15. Frequencies T subpopulation showed an decrement Tregs followed increases Th1 Th17 during progression diabetes.