文章基本信息

标题：Temporal metabolic and transcriptomic characteristics crossing islets and liver reveal dynamic pathophysiology in diet-induced diabetes
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作者：Rui Gao ; Qi Fu ; He-Min Jiang 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：4
页码：1-39
DOI：10.1016/j.isci.2021.102265
语种：English
出版社：Elsevier
摘要：SummaryTo investigate the molecular mechanisms underlying islet dysfunction and insulin resistance in diet-induced diabetes, we conducted temporal RNA sequencing of tissues responsible for insulin secretion (islets) and action (liver) every 4 weeks in mice on high-fat (HFD) or chow diet for 24 weeks, linking to longitudinal profile of metabolic characteristics. The diverse responses of α, β, and δ cells to glucose and palmitate indicated HFD-induced dynamic deterioration of islet function from dysregulation to failure. Insulin resistance developed with variable time course in different tissues. Weighted gene co-expression network analysis and Ingenuity Pathway Analysis implicated islets and liver jointly programmed β-cell compensatory adaption via cell proliferation at early phase and irreversible islet dysfunction by inappropriate immune response at later stage, and identified interconnected molecules including growth differentiation factor 15. Frequencies of T cell subpopulation showed an early decrement in Tregs followed by increases in Th1 and Th17 cells during progression to diabetes.Graphical abstractDisplay OmittedHighlights•Diet-induced diabetes is featured by transition from islet dysfunction to failure•Insulin resistance develops with variable time course in different tissues•Dynamics of islet and liver molecular network interplay at different stages•T-cell-mediated immune response participates via priming and amplification phasesAnimal Physiology ; Diabetology ; Transcriptomics