Type I diabetes mellitus is an autoimmune disease characterized by the destruction of β-cells, leading to severe insulin deficiency. Environmental factors and genetic predisposition are implicated in β-cell destruction, which is the final step in a cascade of complex events. Possible triggers of β-cell destruction are activation of Fas, activation of perforin, increased generation of reactive oxygen species, increased production of inflammatory cytokines, and endoplasmic reticulum (ER) stress. In this study, we examined whether Gryllus bimaculatus (GB) extract could prevent palmitate-induced β-cell apoptosis. Exposure to GB extract prevented palmitate-induced death of MIN6 cells, a mouse pancreatic β-cell line. Palmitate increased total ceramide levels with the elevation of ceramide synthase (CerS)1, CerS4, and CerS6 expressions. Treatment with GB extract decreased the levels and expressions of ceramides related to insulin resistance. CerS4 and CerS6 overexpression, but not CerS1 overexpression, increased palmitate-induced MIN6 cell death by increasing ceramide synthesis. Oppositely, inhibition of ceramide synthesis by fumonisin B1 treatment partially recovered palmitate-induced MIN6 cell death. Furthermore, GB extract reduced ER stress (phosphorylation of PERK and eIF2α), NF-κB–iNOS signaling, and the phosphorylation of MAP kinase (JNK, p38). GB extract reduced pro-apoptotic Bax protein expression but increased anti-apoptotic Bcl2 expression. In addition, CerS4 and CerS6 overexpression aggravated impairment of insulin secretion by palmitate, but GB extract recovered it. In conclusion, GB could be a functional food that improves palmitate-induced β-cell death and insulin secretion.

中文翻译：

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Gryllus bimaculatus 提取物通过抑制神经酰胺合成来防止棕榈酸酯诱导的 β 细胞死亡

I型糖尿病是一种以β细胞破坏为特征的自身免疫性疾病，导致严重的胰岛素缺乏。环境因素和遗传易感性与 β 细胞破坏有关，这是一系列复杂事件的最后一步。β 细胞破坏的可能触发因素是 Fas 的激活、穿孔素的激活、活性氧的产生增加、炎性细胞因子的产生增加和内质网 (ER) 应激。在这项研究中，我们检查了 Gryllus bimaculatus (GB) 提取物是否可以防止棕榈酸酯诱导的 β 细胞凋亡。暴露于 GB 提取物可防止棕榈酸酯诱导的小鼠胰腺 β 细胞系 MIN6 细胞死亡。棕榈酸酯随着神经酰胺合酶 (CerS)1、CerS4 和 CerS6 表达的升高而增加总神经酰胺水平。GB 提取物治疗降低了与胰岛素抵抗相关的神经酰胺的水平和表达。CerS4 和 CerS6 过表达，但不是 CerS1 过表达，通过增加神经酰胺合成增加了棕榈酸酯诱导的 MIN6 细胞死亡。相反，伏马菌素 B1 处理对神经酰胺合成的抑制部分恢复了棕榈酸盐诱导的 MIN6 细胞死亡。此外，GB 提取物降低了 ER 应激（PERK 和 eIF2α 的磷酸化）、NF-κB-iNOS 信号传导和 MAP 激酶（JNK，p38）的磷酸化。GB 提取物降低了促凋亡 Bax 蛋白的表达，但增加了抗凋亡 Bcl2 的表达。此外，CerS4 和 CerS6 过表达加重了棕榈酸酯对胰岛素分泌的损害，但 GB 提取物恢复了它。综上所述，