Overexpression of Insig-1 protects cell against glucolipotoxicity via SREBP-1c

Background: high glucose induced lipid synthesis leads to β cell glucolipotoxicity. sterol regulatory element binding protein-1c (srebp-1c) is reported to be partially involved in this process. insulin induced gene-1 (insig-1) is an important upstream regulator of insig-1-srebps cleavage activating protein (scap)-srebp-1c pathway. insig-1 effectively blocks the transcription of srebp-1c,preventing the activation of the genes for lipid biosynthesis. in this study,we aimed to investigate whether insig-1 protects β cells against glucolipotoxicity. methods. an insig-1 stable cell line was generated by overexpression of insig-1 in ins-1 cells. the expression of insig-1 was evaluated by rt-pcr and western blotting,then,cells were then treated with standard (11.2 mm) or high (25.0 mm) glucose for 0 h,24 h and 72 h. cell viability,apoptosis,glucose stimulated insulin secretion (gsis),lipid metabolism and mrna expression of insulin secretion relevant genes such as irs-2,pdx-1,glut-2,insulin and ucp-2 were evaluated. results: we found that insig-1 suppressed the high glucose induced srebp-1c mrna and protein expression. our results also showed that insig-1 overexpression protected β cells from er stress-induced apoptosis by regulating the proteins expressed in the ire1 α pathway,such as p-ire1α,p-jnk,chop and bcl-2. in addition,insig-1 up-regulated the expression of irs-2,pdx-1,glut-2 and insulin,down-regulated the expression of ucp-2 and improved glucose stimulated insulin secretion (gsis). finally,we found that insig-1 inhibited the lipid accumulation and free fatty acid (ffa) synthesis in a time-dependent manner. conclusions: there results suggest that insig-1 may play a critical role in protecting β cells against glucolipotoxicity by regulating the expression of srebp-1c. © 2011 chen et al; licensee biomed central ltd.