Silibinin protects β cells from glucotoxicity through regulation of the Insig-1/SREBP-1c pathway

Chen,Ke; Zhao,Liling; He,Honghui; Wan,Xinxing; Wang,Fang; Mo,Zhaohui

doi:10.3892/ijmm.2014.1883

Silibinin protects β cells from glucotoxicity through regulation of the Insig-1/SREBP-1c pathway

Authors:
- Ke Chen
- Liling Zhao
- Honghui He
- Xinxing Wan
- Fang Wang
- Zhaohui Mo
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Affiliations: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China
Published online on: August 8, 2014 https://doi.org/10.3892/ijmm.2014.1883
Pages: 1073-1080

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Abstract

Exposure to high glucose may cause glucotoxicity, leading to pancreatic β cell dysfunction including cell apoptosis, impaired glucose‑stimulated insulin secretion (GSIS) and intracellular lipid accumulation. Sterol regulatory element binding protein-1c (SREBP-1c), a key nuclear transcription factor that regulates lipid metabolism, has been proven to play a role in insulin secretion. Insulin induced gene-1 (Insig-1) is an upstream regulatory factor of SREBP-1c. The overexpression of Insig-1 significantly inhibits SREBP-1c expression and thereby blocks the expression of downstream genes. It has been proven that silibinin, a natural flavanone, is involved in a variety of biological functions. In the present study, we examined whether silibinin protects high glucose-induced β cell dysfunction through the Insig-1/SREBP-1c pathway. Our data demonstrated that 30.0 µM of silibinin significantly improved cell viability (P<0.05) after rat insulinoma INS-1 cells were exposed to high glucose for 72 h. Silibinin partially attenuated GSIS following exposure to high glucose for either 24 or 72 h (both P<0.05). As shown by reverse transcription quantitative PCR, silibinin upregulated the mRNA expression of insulin secretion‑related genes [insulin receptor substrate 2 (IRS-2), pancreatic and duodenal homeobox 1 (PDX-1) and insulin], but downregulated uncoupling protein‑2 (UCP-2) expression. Silibinin inhibited intracellular lipid accumulation and free fatty acid (FFA) synthesis. Further experiments revealed that silibinin improved β cell function through the regulation of the Insig-1/SREBP-1c pathway. In conclusion, these results clearly suggest that the protection of β cells from glucotoxicity can be significantly enhanced through the regulation of the Insig-1/SREBP-1c pathway. Thus, silibinin may be a novel therapeutic agent for β cell dysfunction.

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