Department of Nutrition, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou 510080, China.
Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangzhou 510080, China.
Nutrients. 2022 Apr 28;14(9):1835. doi: 10.3390/nu14091835.
Cyanidin-3-O-glucoside (C3G) is a natural colorant with anti-diabetic properties, while its underlying mechanisms remain far from clear. Here, we investigated the protective role of C3G on palmitic acid (PA)-induced pancreatic beta cell dysfunction and further decipher its possible molecular mechanisms. Both primary isolated mouse islets and the INS-1E cell were used, and treated with a mixture of PA (0.5 mM) and C3G (12.5 µM, 25 µM, 50 µM) for different durations (12, 24, 48 h). We found that C3G could dose-dependently ameliorate beta cell secretory function and further alleviate cell apoptosis. Mechanistically, the primary role of the PKR-like ER kinase (PERK) endoplasmic reticulum (ER) stress pathway was detected by RNA sequencing, and the PERK-pathway-related protein expression, especially the pro-apoptotic marker C/EBP homologous protein (CHOP) expression, was significantly downregulated by C3G treatment. The critical role of CHOP in mediating the protective effect of C3G was further validated by small interfering RNA. Conclusively, C3G could ameliorate PA-induced pancreatic beta cell dysfunction targeting the CHOP-related ER stress pathway, which might be used as a nutritional intervention for the preservation of beta cell dysfunction in type 2 diabetes mellitus.
矢车菊素-3-O-葡萄糖苷（C3G）是一种具有抗糖尿病特性的天然着色剂，但其潜在机制仍不清楚。在这里，我们研究了 C3G 对棕榈酸（PA）诱导的胰岛β细胞功能障碍的保护作用，并进一步阐明了其可能的分子机制。我们使用了原代分离的小鼠胰岛和 INS-1E 细胞，并将其与 PA（0.5 mM）和 C3G（12.5 μM、25 μM、50 μM）混合物一起处理不同时间（12、24、48 h）。结果发现，C3G 可剂量依赖性改善β细胞分泌功能，并进一步减轻细胞凋亡。在机制上，通过 RNA 测序检测到 PKR 样内质网激酶（PERK）内质网（ER）应激途径的主要作用，C3G 处理后 PERK 通路相关蛋白表达，特别是促凋亡标志物 C/EBP 同源蛋白（CHOP）表达明显下调。通过小干扰 RNA 进一步验证了 CHOP 在介导 C3G 保护作用中的关键作用。总之，C3G 可以通过 CHOP 相关的 ER 应激途径改善 PA 诱导的胰岛β细胞功能障碍，这可能作为 2 型糖尿病β细胞功能障碍保护的营养干预措施。
