Pancreatic β-cells are critical mediators of glucose homeostasis in the body, and proper cellular nutrient metabolism is critical to β-cell function. Several interacting signaling networks that uniquely control β-cell metabolism produce essential substrates and co-factors for catalytic reactions, including reactions that modify chromatin. Chromatin modifications, in turn, regulate gene expression. The reactions that modify chromatin are therefore well-positioned to adjust gene expression programs according to nutrient availability. It follows that dysregulation of nutrient metabolism in β-cells may impact chromatin state and gene expression through altering the availability of these substrates and co-factors. Metabolic disorders such as type 2 diabetes (T2D) can significantly alter metabolite levels in cells. This suggests that a driver of β-cell dysfunction during T2D may be the altered availability of substrates or co-factors necessary to maintain β-cell chromatin state. Induced changes in the β-cell chromatin modifications may then lead to dysregulation of gene expression, in turn contributing to the downward cascade of events that leads to the loss of functional β-cell mass, and loss of glucose homeostasis, that occurs in T2D.

中文翻译：

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代谢作为 β 细胞染色质状态的中心调节剂

胰腺 β 细胞是体内葡萄糖稳态的关键介质，适当的细胞营养代谢对 β 细胞功能至关重要。几个独特地控制 β 细胞代谢的相互作用信号网络产生催化反应的基本底物和辅助因子，包括修饰染色质的反应。反过来，染色质修饰调节基因表达。因此，修改染色质的反应可以很好地根据营养可用性调整基因表达程序。因此，β细胞中营养代谢的失调可能通过改变这些底物和辅助因子的可用性来影响染色质状态和基因表达。代谢紊乱如 2 型糖尿病 (T2D) 可以显着改变细胞中的代谢物水平。这表明 T2D 期间 β 细胞功能障碍的驱动因素可能是维持 β 细胞染色质状态所需的底物或辅因子的可用性改变。β 细胞染色质修饰的诱导变化然后可能导致基因表达失调，进而导致事件的向下级联，导致功能性 β 细胞质量的丧失和葡萄糖稳态的丧失，这在 T2D 中发生。