- 作者: Ke Chen; Ping Jin; Hong-hui He; Yan-hong Xie; Xiao-yun Xie; Zhao-hui Mo
- 作者服務機構: Department of Endocrinology, Third Xiangya Hospital of Central South University, Changsha, Mainland China
- 中文摘要: --
- 英文摘要:
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
IRE1α 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. - 中文關鍵字: --
- 英文關鍵字: --