tailieunhanh - Báo cáo y học: " Overexpression of Insig-1 protects b cell against glucolipotoxicity via SREBP-1c"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: Overexpression of Insig-1 protects b cell against glucolipotoxicity via SREBP-1c. | Chen et al. Journal of Biomedical Science 2011 18 57 http content 18 1 57 The cost of publication in Journal of Biomedical Science Is borne by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Overexpression of Insig-1 protects b cell against glucolipotoxicity via SREBP-1c Ke Chen ping jin Hong-hui He Yan-hong Xie Xiao-yun Xie and Zhao-hui Mo Abstract Background High glucose induced lipid synthesis leads to b 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 b 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 mM or high 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 b cells from ER stress-induced apoptosis by regulating the proteins expressed in the IRE1a pathway such as p-IRE1a 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 .