title: Silibinin protects β cells from glucotoxicity through regulation of the Insig-1/SREBP-1c pathway.
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.
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Liling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Honghui
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Xinxing
authors.initials: X
authors.lastname: Wan
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Mo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D005227:Fatty Acids / Q000096:biosynthesis; D005947:Glucose / Q000633:toxicity*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000473:pathology*; D047908:Intracellular Signaling Peptides and Proteins; D066292:Lipid Droplets / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; C491574:Insig1 protein, rat; D007328:Insulin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D012838:Silymarin; D051780:Sterol Regulatory Element Binding Protein 1; D000077385:Silybin; D005947:Glucose