Department of Geriatrics, Ninth Hospital of Xi'an, No. 151, East Section of South 2nd Ring Road, Xi'an, Shaanxi, China.
Department of Orthopedics, Ninth Hospital of Xi'an, Xi'an, Shaanxi, China.
Genes Genomics. 2022 Jul;44(7):867-878. doi: 10.1007/s13258-022-01250-z. Epub 2022 May 28.
Destruction of pancreatic beta cells is the most typical characteristic of diabetes.
We aimed to evaluate the effect of berberine (BBR), a bioactive isoquinoline derivative alkaloid, on beta cell injury.
Rodent pancreatic beta cell line INS-1 was treated with 0.5 mM palmitate (PA) for 24 h to establish an in vitro beta cell injury model.
BBR at 5 µM promoted cell viability, inhibited cell apoptosis and enhanced insulin secretion in PA-induced INS-1 cells. BBR treatment also suppressed PA-induced oxidative stress in INS-1 cells, as evidenced by the decreased ROS production and increased activities of antioxidant enzymes. In addition, suppressed ATP production and reduced mitochondrial membrane potential were restored by BBR in PA-treated INS-1 cells. It was further determined that BBR affected the expressions of mitophagy-associated proteins, suggesting that BBR promoted mitophagy in PA-exposed INS-1 cells. Meanwhile, we found that BBR facilitated nuclear expression and DNA-binding activity of Nrf2, an antioxidative protein that can regulate mitophagy. Finally, a rescue experiment was performed and the results demonstrated that the effect of BBR on cell viability, apoptosis and mitochondrial function in PA-induced INS-1 cells were cancelled by PINK1 knockdown.
BBR protects islet β cells from PA-induced injury, and this protective effect may be achieved by regulating mitophagy. The present study may provide a novel therapeutic strategy for β cell injury in diabetes mellitus.
胰腺β细胞的破坏是糖尿病最典型的特征。
我们旨在评估黄连素（BBR），一种生物活性异喹啉衍生生物碱，对β细胞损伤的作用。
用 0.5 mM 棕榈酸（PA）处理啮齿动物胰腺β细胞系 INS-1 24 h，建立体外β细胞损伤模型。
5 μM 的 BBR 可促进细胞活力，抑制细胞凋亡，并增强 PA 诱导的 INS-1 细胞胰岛素分泌。BBR 处理还抑制了 INS-1 细胞中的 PA 诱导的氧化应激，表现为 ROS 产生减少和抗氧化酶活性增加。此外，BBR 恢复了 PA 处理的 INS-1 细胞中受抑制的 ATP 产生和降低的线粒体膜电位。进一步确定 BBR 影响了自噬相关蛋白的表达，表明 BBR 促进了 PA 暴露的 INS-1 细胞中的自噬。同时，我们发现 BBR 促进了抗氧化蛋白 Nrf2 的核表达和 DNA 结合活性，Nrf2 可调节自噬。最后进行了挽救实验，结果表明，BBR 对 PA 诱导的 INS-1 细胞活力、凋亡和线粒体功能的影响被 PINK1 敲低所取消。
BBR 可保护胰岛β细胞免受 PA 诱导的损伤，这种保护作用可能是通过调节自噬实现的。本研究可能为糖尿病β细胞损伤提供一种新的治疗策略。
