Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.

中文翻译：

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单个小鼠 β 细胞的同步加速器荧光成像揭示了低度炎症模型中锌、钙和铁的变化。

胰腺β细胞合成和分泌维持机体能量平衡的胰岛素。在人类中，β 细胞功能障碍和死亡有助于 2 型糖尿病 (T2D) 的发病机制。尽管 β 细胞功能障碍的原因很复杂，但肥胖引起的低度全身炎症也起作用。例如，表现出促炎细胞因子 IL-6 和 IL-1beta 水平升高的肥胖个体具有更高的 β 细胞功能障碍和 T2D 风险。有趣的是，肥胖引起的炎症改变了几种细胞金属调节基因的表达，促使本研究检查暴露于促炎细胞因子后 β 细胞金属组的变化。将原代小鼠 β 细胞暴露于 IL-6 和 IL-1β 的组合中 48 小时，通过同步加速器X射线荧光显微镜进行化学固定和成像。定量分析显示锌的平均总细胞含量惊人地减少了 2.4 倍，从 158 ± 57.7 飞克 (fg) 降至 65.7 ± 29.7 fg；钙从 216 ± 67.4 下降到 154.3 ± 68.7 fg（分别为对照与细胞因子）。细胞因子处理后，平均总细胞铁含量从 30.4 ± 12.2 略微增加至 47.2 ± 36.4 fg；一个细胞亚群（38%）表现出更大的铁密度增加。在细胞因子暴露后观察到锌和钙的亚细胞分布的变化。β 细胞含有大量的铁点，这些点在接触细胞因子后会积累更多的铁。