Department of Surgery, Ray Rajotte Surgical-Medical Research Institute, Alberta Diabetes Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
Division of General Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
PLoS One. 2021 Oct 6;16(10):e0258208. doi: 10.1371/journal.pone.0258208. eCollection 2021.
Islet transplantation is being considered as an alternative treatment for type 1 diabetes. Despite recent progress, transplant recipients continue to experience progressive loss of insulin independence. Cyanidin-3-O-Glucoside (C3G) has shown to be protective against damage that may lead to post-transplant islet loss. In this study, human islets cultured with or without C3G were treated with human amylin, Aβ1-42, H2O2, or rapamycin to mimic stresses encountered in the post-transplant environment. Samples of these islets were collected and assayed to determine C3G's effect on cell viability and function, reactive oxygen species (ROS), oxidative stress, amyloid formation, and the presence of inflammatory as well as autophagic markers. C3G treatment of human islets exposed to either amylin or Aβ1-42 increased cell viability (p<0.01) and inhibited amyloid formation (p<0.01). A reduction in ROS and an increase in HO-1 gene expression as well as in vitro islet function were also observed in C3G-treated islets exposed to amylin or Aβ1-42, although not significantly. Additionally, treatment with C3G resulted in a significant reduction in the protein expression of inflammatory markers IL-1β and NLRP3 (p<0.01) as well as an increase in LC3 autophagic marker (p<0.05) in human islets treated with amylin, Aβ1-42, rapamycin, or H2O2. Thus, C3G appears to have a multi-faceted protective effect on human islets in vitro, possibly through its anti-oxidant property and alteration of inflammatory as well as autophagic pathways.
胰岛移植被认为是治疗 1 型糖尿病的一种替代疗法。尽管最近取得了进展,但移植受者仍会经历胰岛素独立性的逐渐丧失。矢车菊素-3-O-葡萄糖苷 (C3G) 已被证明可防止可能导致移植后胰岛丧失的损伤。在这项研究中,用人胰岛与或不与 C3G 一起培养,并用人胰岛淀粉样多肽、Aβ1-42、H2O2 或雷帕霉素处理,以模拟移植后环境中遇到的应激。收集这些胰岛的样本并进行检测,以确定 C3G 对细胞活力和功能、活性氧 (ROS)、氧化应激、淀粉样形成以及炎症和自噬标志物的存在的影响。用 C3G 处理暴露于淀粉样多肽或 Aβ1-42 的人胰岛可增加细胞活力 (p<0.01) 并抑制淀粉样形成 (p<0.01)。在 C3G 处理的暴露于淀粉样多肽或 Aβ1-42 的胰岛中也观察到 ROS 减少和 HO-1 基因表达增加以及体外胰岛功能增强,尽管不显著。此外,用 C3G 处理还导致暴露于淀粉样多肽、Aβ1-42、雷帕霉素或 H2O2 的人胰岛中炎症标志物 IL-1β 和 NLRP3 的蛋白表达显著减少 (p<0.01) 以及 LC3 自噬标志物增加 (p<0.05)。因此,C3G 似乎对体外人胰岛具有多方面的保护作用,可能通过其抗氧化特性以及改变炎症和自噬途径。