KMID : 0606920200280020163
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Biomolecules & Therapeutics 2020 Volume.28 No. 2 p.163 ~ p.171
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Involvement of Estrogen Receptor-¥á in the Activation of Nrf2-Antioxidative Signaling Pathways by Silibinin in Pancreatic ¥â-Cells
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Chu Chun
Gao Xiang Li Xiang Zhang Xiaoying Ma Ruixin Jia Ying Li Dahong Wang Dongkai Xu Fanxing
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Abstract
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Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic ¥â-cells through up-regulation of estrogen receptor-¥á (ER¥á) expression. However, the underlying protective mechanism of silibinin in pancreatic ¥â-cells is still unclear. In the current study, we sought to determine whether ER¥á acts as the target of silibinin for the modulation of antioxidative response in pancreatic ¥â-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin- induced type 2 diabetic rats. Moreover, expression of ER¥á, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic ¥â-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 ¥ìM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ER¥á, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ER¥á antagonist (MPP) in INS-1 cells or silencing ER¥á expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic ¥â-cells through regulation of ER¥á expression.
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KEYWORD
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Diabetes mellitus, Silibinin, Pancreatic ¥â-cell, Estrogen receptor-¥á, Antioxidative response
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