Verbascoside Protects Pancreatic β-Cells against ER-Stress

• Published in: Biomedicines Vol. 8; no. 12; p. 582
• Main Authors: Galli, Alessandra, Marciani, Paola, Marku, Algerta, Ghislanzoni, Silvia, Bertuzzi, Federico, Rossi, Raffaella, Di Giancamillo, Alessia, Castagna, Michela, Perego, Carla
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.12.2020; MDPI
• Subjects: Antibodies; Antioxidants; Apoptosis; Beta cells; Cell survival; Cloning; Cytokines; Diabetes; Diabetes mellitus (non-insulin dependent); Endoplasmic reticulum; Enzymes; Epidemiology; Experiments; Flow cytometry; Glucose; Hyperglycemia; Inflammation; Insulin; Insulin resistance; insulin-producing cells; Metabolism; Mitochondria; Neuroprotection; Olive oil; Oxidative stress; Pancreas; Penicillin; Polyphenols; Protein folding; Protein kinase; Proteins; Ribonucleic acid; RNA; UPR; verbascoside; Italy; St Louis Missouri; United Kingdom > UK; United States > US; verbascoside; polyphenols; insulin-producing cells; ER-stress; UPR; mitochondria; anti-inflammatory; PERK; diabetes; oxidative stress
• ISSN: 2227-9059; 2227-9059
• 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.