Galli Alessandra, Marciani Paola, Marku Algerta, Ghislanzoni Silvia, Bertuzzi Federico, Rossi Raffaella, Di Giancamillo Alessia, Castagna Michela, Perego Carla
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20134 Milan, Italy.
Diabetology Unit, Niguarda Hospital, 20162 Milan, Italy.
Biomedicines. 2020 Dec 8;8(12):582. doi: 10.3390/biomedicines8120582.
Substantial epidemiological evidence indicates that a diet rich in polyphenols protects against developing type 2 diabetes. The phenylethanoid glycoside verbascoside/acteoside, a widespread polyphenolic plant compound, has several biological properties including strong antioxidant, anti-inflammatory and neuroprotective activities. The aim of this research was to test the possible effects of verbascoside on pancreatic β-cells, a target never tested before. Mouse and human β-cells were incubated with verbascoside (0.8-16 µM) for up to five days and a combination of biochemical and imaging techniques were used to assess the β-cell survival and function under normal or endoplasmic reticulum (ER)-stress inducing conditions. We found a dose-dependent protective effect of verbascoside against oxidative stress in clonal and human β-cells. Mechanistic studies revealed that the polyphenol protects β-cells against ER-stress mediated dysfunctions, modulating the activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK) branch of the unfolded protein response and promoting mitochondrial dynamics. As a result, increased viability, mitochondrial function and insulin content were detected in these cells. These studies provide the evidence that verbascoside boosts the ability of β-cells to cope with ER-stress, an important contributor of β-cell dysfunction and failure in diabetic conditions and support the therapeutic potential of verbascoside in diabetes.
大量流行病学证据表明，富含多酚的饮食可预防2型糖尿病的发生。苯乙醇苷类毛蕊花糖苷/异毛蕊花糖苷是一种广泛存在的多酚类植物化合物，具有多种生物学特性，包括强大的抗氧化、抗炎和神经保护活性。本研究的目的是测试毛蕊花糖苷对胰腺β细胞的可能作用，此前从未有过相关研究。将小鼠和人类β细胞与毛蕊花糖苷（0.8 - 16 μM）孵育长达五天，并使用生化和成像技术相结合的方法，评估正常或内质网（ER）应激诱导条件下β细胞的存活和功能。我们发现毛蕊花糖苷对克隆和人类β细胞的氧化应激具有剂量依赖性保护作用。机制研究表明，这种多酚可保护β细胞免受ER应激介导的功能障碍，调节未折叠蛋白反应中蛋白激酶RNA样内质网激酶（PERK）分支的激活，并促进线粒体动力学。结果，在这些细胞中检测到活力增加、线粒体功能和胰岛素含量增加。这些研究提供了证据，表明毛蕊花糖苷可增强β细胞应对ER应激的能力，ER应激是糖尿病状态下β细胞功能障碍和衰竭的重要原因，并支持毛蕊花糖苷在糖尿病治疗中的潜力。
