PURPOSE Type 2 diabetes mellitus is characterized by insulin resistance and β-cell dysfunction. Elevated free fatty acids-induced lipotoxicity may play a vital role in the pathogenesis of β-cell insulin resistance. Exercise-stimulated myokine irisin has been reported to be closely related to T2DM. However, its function on β-cell insulin signaling and the underlying mechanisms are only partially elucidated as yet. METHODS High-fat diet-fed C57BL/6J mice and palmitic acid-treated MIN6 cell models were utilized as lipotoxic models. Factors associated with β-cell insulin signaling transduction and inflammatory responses were assessed in these models. Furthermore, the role of irisin in β-cells and the underlying mechanisms were also explored. RESULTS Irisin effectively decreased lipid levels in HFD mice, enhanced glucose-stimulated insulin secretion and nullified the expressions of inflammatory cytokines in vivo and in vitro experiments. Moreover, irisin improved PI3K/AKT insulin signaling pathway and inhibited TLR4/NF-κB inflammatory signaling pathway in both islets of HFD mice and PA-treated MIN6 cells. Mechanistic analysis indicated that FOXO1 might serve as a bridge between the two pathways. CONCLUSION Irisin alleviates lipotoxicity-induced β-cell insulin resistance and inflammatory response through the activation of PI3K/AKT/FOXO1 signaling pathways and the inhibition of TLR4/NF-κB signaling pathways. Irisin might provide a novel therapeutic strategy for T2DM.

中文翻译：

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Irisin 通过激活 PI3K/AKT/FOXO1 信号通路减轻 FFA 诱导的 β 细胞胰岛素抵抗和炎症反应。

目的 2 型糖尿病的特点是胰岛素抵抗和 β 细胞功能障碍。升高的游离脂肪酸诱导的脂毒性可能在 β 细胞胰岛素抵抗的发病机制中起重要作用。据报道，运动刺激的肌动蛋白鸢尾素与 T2DM 密切相关。然而，其对 β 细胞胰岛素信号传导的功能及其潜在机制目前仅部分阐明。方法采用高脂饮食喂养的C57BL/6J小鼠和棕榈酸处理的MIN6细胞模型作为脂毒性模型。在这些模型中评估了与 β 细胞胰岛素信号转导和炎症反应相关的因素。此外，还探讨了鸢尾素在 β 细胞中的作用及其潜在机制。结果 Irisin 有效降低了 HFD 小鼠的血脂水平，在体内和体外实验中增强葡萄糖刺激的胰岛素分泌并消除炎性细胞因子的表达。此外，鸢尾素改善了 HFD 小鼠胰岛和 PA 处理的 MIN6 细胞中的 PI3K/AKT 胰岛素信号通路并抑制了 TLR4/NF-κB 炎症信号通路。机理分析表明，FOXO1 可能充当这两种途径之间的桥梁。结论鸢尾素通过激活PI3K/AKT/FOXO1信号通路和抑制TLR4/NF-κB信号通路来减轻脂毒性诱导的β细胞胰岛素抵抗和炎症反应。Irisin 可能为 T2DM 提供一种新的治疗策略。irisin 改善了 HFD 小鼠胰岛和 PA 处理的 MIN6 细胞中的 PI3K/AKT 胰岛素信号通路并抑制 TLR4/NF-κB 炎症信号通路。机理分析表明，FOXO1 可能充当这两种途径之间的桥梁。结论鸢尾素通过激活PI3K/AKT/FOXO1信号通路和抑制TLR4/NF-κB信号通路来减轻脂毒性诱导的β细胞胰岛素抵抗和炎症反应。Irisin 可能为 T2DM 提供一种新的治疗策略。irisin 改善了 HFD 小鼠胰岛和 PA 处理的 MIN6 细胞中的 PI3K/AKT 胰岛素信号通路并抑制 TLR4/NF-κB 炎症信号通路。机理分析表明，FOXO1 可能充当这两种途径之间的桥梁。结论鸢尾素通过激活PI3K/AKT/FOXO1信号通路和抑制TLR4/NF-κB信号通路来减轻脂毒性诱导的β细胞胰岛素抵抗和炎症反应。Irisin 可能为 T2DM 提供一种新的治疗策略。结论鸢尾素通过激活PI3K/AKT/FOXO1信号通路和抑制TLR4/NF-κB信号通路来减轻脂毒性诱导的β细胞胰岛素抵抗和炎症反应。Irisin 可能为 T2DM 提供一种新的治疗策略。结论鸢尾素通过激活PI3K/AKT/FOXO1信号通路和抑制TLR4/NF-κB信号通路来减轻脂毒性诱导的β细胞胰岛素抵抗和炎症反应。Irisin 可能为 T2DM 提供一种新的治疗策略。